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Guggisberg, Ann M., Rachel E. Amthor y Audrey R. Odom. "Isoprenoid Biosynthesis in Plasmodium falciparum". Eukaryotic Cell 13, n.º 11 (12 de septiembre de 2014): 1348–59. http://dx.doi.org/10.1128/ec.00160-14.
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ABSTRACTMalaria kills nearly 1 million people each year, and the protozoan parasitePlasmodium falciparumhas become increasingly resistant to current therapies. Isoprenoid synthesis via the methylerythritol phosphate (MEP) pathway represents an attractive target for the development of new antimalarials. The phosphonic acid antibiotic fosmidomycin is a specific inhibitor of isoprenoid synthesis and has been a helpful tool to outline the essential functions of isoprenoid biosynthesis inP. falciparum. Isoprenoids are a large, diverse class of hydrocarbons that function in a variety of essential cellular processes in eukaryotes. InP. falciparum, isoprenoids are used for tRNA isopentenylation and protein prenylation, as well as the synthesis of vitamin E, carotenoids, ubiquinone, and dolichols. Recently, isoprenoid synthesis inP. falciparumhas been shown to be regulated by a sugar phosphatase. We outline what is known about isoprenoid function and the regulation of isoprenoid synthesis inP. falciparum, in order to identify valuable directions for future research.
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De Lillis, Manuela, Pietro Massimiliano Bianco y Francesco Loreto. "The influence of leaf water content and isoprenoids on flammability of some Mediterranean woody species". International Journal of Wildland Fire 18, n.º 2 (2009): 203. http://dx.doi.org/10.1071/wf07075.
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The impact of water content and isoprenoids on leaf flammability was studied. Field and laboratory experiments were carried out on monoterpene-emitting evergreen broad-leaved species (Quercus ilex, Quercus suber); a needle-leaved species (Pinus halepensis) that emits and stores monoterpenes; an evergreen species (Myrtus communis) that emits isoprene but stores monoterpenes; and a deciduous species (Quercus pubescens) that emits isoprene. Photosynthesis, leaf water content (LWC) and isoprenoid emission were measured. Isoprenoid content was calculated. Temperatures of visible smoke, incandescence and flame appearance were recorded. The LWC significantly correlated with both photosynthesis and isoprenoid emissions. Linear correlation and factorial analysis revealed a positive correlation between temperature of flame appearance and LWC and a negative relationship between temperature of flame appearance and isoprenoid emission. Multiple regression analysis indicated that the temperature of flame appearance was reduced in broadleaved monoterpene-emitting species. In monoterpene emitters, the temperature of flame appearance depended for ~65% on LWC, whereas monoterpene emissions explained ~35% of the dependency. P. halepensis and M. communis, storing high levels of isoprenoids, ignited at high humidity. The results may be explained if isoprenoids indeed facilitate leaf ignition but, being dissolved in water, isoprenoids are also an indicator of a high water content that decreases flammability.
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Chatzivasileiou, Alkiviadis Orfefs, Valerie Ward, Steven McBride Edgar y Gregory Stephanopoulos. "Two-step pathway for isoprenoid synthesis". Proceedings of the National Academy of Sciences 116, n.º 2 (24 de diciembre de 2018): 506–11. http://dx.doi.org/10.1073/pnas.1812935116.
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Isoprenoids comprise a large class of chemicals of significant interest due to their diverse properties. Biological production of isoprenoids is considered to be the most efficient way for their large-scale production. Isoprenoid biosynthesis has thus far been dependent on pathways inextricably linked to glucose metabolism. These pathways suffer from inherent limitations due to their length, complex regulation, and extensive cofactor requirements. Here, we present a synthetic isoprenoid pathway that aims to overcome these limitations. This isopentenol utilization pathway (IUP) can produce isopentenyl diphosphate or dimethylallyl diphosphate, the main precursors to isoprenoid synthesis, through sequential phosphorylation of isopentenol isomers isoprenol or prenol. After identifying suitable enzymes and constructing the pathway, we attempted to probe the limits of the IUP for producing various isoprenoid downstream products. The IUP flux exceeded the capacity of almost all downstream pathways tested and was competitive with the highest isoprenoid fluxes reported.
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Mu, Zhaobin, Joan Llusià y Josep Peñuelas. "Ground Level Isoprenoid Exchanges Associated with Pinus pinea Trees in A Mediterranean Turf". Atmosphere 11, n.º 8 (31 de julio de 2020): 809. http://dx.doi.org/10.3390/atmos11080809.
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The emissions of isoprenoids, a kind of biogenic volatile organic compounds (BVOCs), from soils is not well characterized. We quantified the exchange of isoprenoids between soil with litter and atmosphere along a horizontal gradient from the trunks of the trees, in a Mediterranean Pinus pinea plantation with dry and green needle litter to open herbaceous turf during mornings at mid-summer. Further, potential associated drivers were identified. Isoprenoid emissions were greatest and most diverse, and also can be roughly estimated by litter dry weight near the trunk, where the needle litter was denser. The composition of emitted isoprenoid by needle litter was different than the composition previously described for green needles. Low exchange rates of isoprenoids were recorded in open turf. Isoprenoid exchange rates were correlated positively with soil temperature and negatively with soil moisture. Given the variations in ground emissions with soil, vegetation, microorganisms, and associated interactions, we recommend widespread extensive spatio-temporal analysis of ground level BVOC exchanges in the different ecosystem types.
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Phulara, Suresh Chandra, Preeti Chaturvedi y Pratima Gupta. "Isoprenoid-Based Biofuels: Homologous Expression and Heterologous Expression in Prokaryotes". Applied and Environmental Microbiology 82, n.º 19 (15 de julio de 2016): 5730–40. http://dx.doi.org/10.1128/aem.01192-16.
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ABSTRACTEnthusiasm for mining advanced biofuels from microbial hosts has increased remarkably in recent years. Isoprenoids are one of the highly diverse groups of secondary metabolites and are foreseen as an alternative to petroleum-based fuels. Most of the prokaryotes synthesize their isoprenoid backbone via the deoxyxylulose-5-phosphate pathway from glyceraldehyde-3-phosphate and pyruvate, whereas eukaryotes synthesize isoprenoids via the mevalonate pathway from acetyl coenzyme A (acetyl-CoA). Microorganisms do not accumulate isoprenoids in large quantities naturally, which restricts their application for fuel purposes. Various metabolic engineering efforts have been utilized to overcome the limitations associated with their natural and nonnatural production. The introduction of heterologous pathways/genes and overexpression of endogenous/homologous genes have shown a remarkable increase in isoprenoid yield and substrate utilization in microbial hosts. Such modifications in the hosts' genomes have enabled researchers to develop commercially competent microbial strains for isoprenoid-based biofuel production utilizing a vast array of substrates. The present minireview briefly discusses the recent advancement in metabolic engineering efforts in prokaryotic hosts for the production of isoprenoid-based biofuels, with an emphasis on endogenous, homologous, and heterologous expression strategies.
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Choi, Bo Hyun, Hyun Joon Kang, Sun Chang Kim y Pyung Cheon Lee. "Organelle Engineering in Yeast: Enhanced Production of Protopanaxadiol through Manipulation of Peroxisome Proliferation in Saccharomyces cerevisiae". Microorganisms 10, n.º 3 (18 de marzo de 2022): 650. http://dx.doi.org/10.3390/microorganisms10030650.
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Isoprenoids, which are natural compounds with diverse structures, possess several biological activities that are beneficial to humans. A major consideration in isoprenoid production in microbial hosts is that the accumulation of biosynthesized isoprenoid within intracellular membranes may impede balanced cell growth, which may consequently reduce the desired yield of the target isoprenoid. As a strategy to overcome this suggested limitation, we selected peroxisome membranes as depots for the additional storage of biosynthesized isoprenoids to facilitate increased isoprenoid production in Saccharomyces cerevisiae. To maximize the peroxisome membrane storage capacity of S.cerevisiae, the copy number and size of peroxisomes were increased through genetic engineering of the expression of three peroxisome biogenesis-related peroxins (Pex11p, Pex34p, and Atg36p). The genetically enlarged and high copied peroxisomes in S.cerevisiae were stably maintained under a bioreactor fermentation condition. The peroxisome-engineered S.cerevisiae strains were then utilized as host strains for metabolic engineering of heterologous protopanaxadiol pathway. The yields of protopanaxadiol from the engineered peroxisome strains were ca 78% higher than those of the parent strain, which strongly supports the rationale for harnessing the storage capacity of the peroxisome membrane to accommodate the biosynthesized compounds. Consequently, this study presents in-depth knowledge on peroxisome biogenesis engineering in S.cerevisiae and could serve as basic information for improvement in ginsenosides production and as a potential platform to be utilized for other isoprenoids.
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Pérez-Gil, Jordi y Manuel Rodríguez-Concepción. "Metabolic plasticity for isoprenoid biosynthesis in bacteria". Biochemical Journal 452, n.º 1 (25 de abril de 2013): 19–25. http://dx.doi.org/10.1042/bj20121899.
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Isoprenoids are a large family of compounds synthesized by all free-living organisms. In most bacteria, the common precursors of all isoprenoids are produced by the MEP (methylerythritol 4-phosphate) pathway. The MEP pathway is absent from archaea, fungi and animals (including humans), which synthesize their isoprenoid precursors using the completely unrelated MVA (mevalonate) pathway. Because the MEP pathway is essential in most bacterial pathogens (as well as in the malaria parasites), it has been proposed as a promising new target for the development of novel anti-infective agents. However, bacteria show a remarkable plasticity for isoprenoid biosynthesis that should be taken into account when targeting this metabolic pathway for the development of new antibiotics. For example, a few bacteria use the MVA pathway instead of the MEP pathway, whereas others possess the two full pathways, and some parasitic strains lack both the MVA and the MEP pathways (probably because they obtain their isoprenoids from host cells). Moreover, alternative enzymes and metabolic intermediates to those of the canonical MVA or MEP pathways exist in some organisms. Recent work has also shown that resistance to a block of the first steps of the MEP pathway can easily be developed because several enzymes unrelated to isoprenoid biosynthesis can produce pathway intermediates upon spontaneous mutations. In the present review, we discuss the major advances in our knowledge of the biochemical toolbox exploited by bacteria to synthesize the universal precursors for their essential isoprenoids.
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Moehninsi, Iris Lange, B. Markus Lange y Duroy A. Navarre. "Altering potato isoprenoid metabolism increases biomass and induces early flowering". Journal of Experimental Botany 71, n.º 14 (16 de abril de 2020): 4109–24. http://dx.doi.org/10.1093/jxb/eraa185.
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Abstract Isoprenoids constitute the largest class of plant natural products and have diverse biological functions including in plant growth and development. In potato (Solanum tuberosum), the regulatory mechanism underlying the biosynthesis of isoprenoids through the mevalonate pathway is unclear. We assessed the role of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) homologs in potato development and in the metabolic regulation of isoprenoid biosynthesis by generating transgenic lines with down-regulated expression (RNAi-hmgr) or overexpression (OE) of one (StHMGR1 or StHMGR3) or two genes, HMGR and farnesyl diphosphate synthase (FPS; StHMGR1/StFPS1 or StHMGR3/StFPS1). Levels of sterols, steroidal glycoalkaloids (SGAs), and plastidial isoprenoids were elevated in the OE-HMGR1, OE-HMGR1/FPS1, and OE-HMGR3/FPS1 lines, and these plants exhibited early flowering, increased stem height, increased biomass, and increased total tuber weight. However, OE-HMGR3 lines showed dwarfism and had the highest sterol amounts, but without an increase in SGA levels, supporting a rate-limiting role for HMGR3 in the accumulation of sterols. Potato RNAi-hmgr lines showed inhibited growth and reduced cytosolic isoprenoid levels. We also determined the relative importance of transcriptional control at regulatory points of isoprenoid precursor biosynthesis by assessing gene–metabolite correlations. These findings provide novel insights into specific end-products of the sterol pathway and could be important for crop yield and bioenergy crops.
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Junker-Frohn, Laura Verena, Anita Kleiber, Kirstin Jansen, Arthur Gessler, Jürgen Kreuzwieser y Ingo Ensminger. "Differences in isoprenoid-mediated energy dissipation pathways between coastal and interior Douglas-fir seedlings in response to drought". Tree Physiology 39, n.º 10 (1 de octubre de 2019): 1750–66. http://dx.doi.org/10.1093/treephys/tpz075.
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ABSTRACT Plants have evolved energy dissipation pathways to reduce photooxidative damage under drought when photosynthesis is hampered. Non-volatile and volatile isoprenoids are involved in non-photochemical quenching of excess light energy and scavenging of reactive oxygen species. A better understanding of trees’ ability to cope with and withstand drought stress will contribute to mitigate the negative effects of prolonged drought periods expected under future climate conditions. Therefore we investigated if Douglas-fir (Pseudotsuga menziesii(Mirb.)) provenances from habitats with contrasting water availability reveal intraspecific variation in isoprenoid-mediated energy dissipation pathways. In a controlled drought experiment with 1-year-old seedlings of an interior and a coastal Douglas-fir provenance, we assessed the photosynthetic capacity, pool sizes of non-volatile isoprenoids associated with the photosynthetic apparatus, as well as pool sizes and emission of volatile isoprenoids. We observed variation in the amount and composition of non-volatile and volatile isoprenoids among provenances, which could be linked to variation in photosynthetic capacity under drought. The coastal provenance exhibited an enhanced biosynthesis and emission of volatile isoprenoids, which is likely sustained by generally higher assimilation rates under drought. In contrast, the interior provenance showed an enhanced photoprotection of the photosynthetic apparatus by generally higher amounts of non-volatile isoprenoids and increased amounts of xanthophyll cycle pigments under drought. Our results demonstrate that there is intraspecific variation in isoprenoid-mediated energy dissipation pathways among Douglas-fir provenances, which may be important traits when selecting provenances suitable to grow under future climate conditions.
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DISCH, Andrea, Jörg SCHWENDER, Christian MÜLLER, Hartmut K. LICHTENTHALER y Michel ROHMER. "Distribution of the mevalonate and glyceraldehyde phosphate/pyruvate pathways for isoprenoid biosynthesis in unicellular algae and the cyanobacterium Synechocystis PCC 6714". Biochemical Journal 333, n.º 2 (15 de julio de 1998): 381–88. http://dx.doi.org/10.1042/bj3330381.
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Isopentenyl diphosphate, the universal isoprenoid precursor, can be produced by two different biosynthetic routes: either via the acetate/mevalonate (MVA) pathway, or via the more recently identified MVA-independent glyceraldehyde phosphate/pyruvate pathway. These two pathways are easily differentiated by incorporation of [1-13C]glucose and analysis of the resulting labelling patterns found in the isoprenoids. This method was successfully applied to several unicellular algae raised under heterotrophic growth conditions and allowed for the identification of the pathways that were utilized for isoprenoid biosynthesis. All isoprenoids examined (sterols, phytol, carotenoids) of the green algae Chlorella fusca and Chlamydomonas reinhardtii were synthesized via the GAP/pyruvate pathway, as in another previously investigated green alga, Scenedesmus obliquus, which was also shown in this study to synthesize ubiquinone by the same MVA-independent route. In the red alga Cyanidium caldarium and in the Chrysophyte Ochromonas danica a clear dichotomy was observed: as in higher plants, sterols were formed via the MVA route, whereas chloroplast isoprenoids (phytol in Cy. caldariumand O. danica and β-carotene in O. danica) were synthesized via the GAP/pyruvate route. In contrast, the Euglenophyte Euglena gracilis synthesized ergosterol, as well as phytol, via the acetate/MVA route. Similar feeding experiments were performed with the cyanobacterium SynechocystisPCC 6714 using [1-13C]- and [6-13C]-glucose. The two isoprenoids examined, phytol and β-carotene, were shown to have the typical labelling pattern derived from the GAP/pyruvate route.
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Balibar, Carl J., Xiaoyu Shen y Jianshi Tao. "The Mevalonate Pathway of Staphylococcus aureus". Journal of Bacteriology 191, n.º 3 (21 de noviembre de 2008): 851–61. http://dx.doi.org/10.1128/jb.01357-08.
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ABSTRACT Isoprenoids are a class of ubiquitous organic molecules synthesized from the five-carbon starter unit isopentenyl pyrophosphate (IPP). Comprising more than 30,000 known natural products, isoprenoids serve various important biological functions in many organisms. In bacteria, undecaprenyl pyrophosphate is absolutely required for the formation of cell wall peptidoglycan and other cell surface structures, while ubiquinones and menaquinones, both containing an essential prenyl moiety, are key electron carriers in respiratory energy generation. There is scant knowledge on the nature and regulation of bacterial isoprenoid pathways. In order to explore the cellular responses to perturbations in the mevalonate pathway, responsible for producing the isoprenoid precursor IPP in many gram-positive bacteria and eukaryotes, we constructed three strains of Staphylococcus aureus in which each of the mevalonate pathway genes is regulated by an IPTG (isopropyl-β-d-thiogalactopyranoside)-inducible promoter. We used DNA microarrays to profile the transcriptional effects of downregulating the components of the mevalonate pathway in S. aureus and demonstrate that decreased expression of the mevalonate pathway leads to widespread downregulation of primary metabolism genes, an upregulation in virulence factors and cell wall biosynthetic determinants, and surprisingly little compensatory expression in other isoprenoid biosynthetic genes. We subsequently correlate these transcriptional changes with downstream metabolic consequences.
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Gölz, Peter y Jürgen Feierabend. "Isoprenoid Biosynthesis and Stability in Developing Green and Achlorophyllous Leaves of Rye (Secale cereale L.)". Zeitschrift für Naturforschung C 48, n.º 11-12 (1 de diciembre de 1993): 886–95. http://dx.doi.org/10.1515/znc-1993-11-1212.
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Formation of major prenylquinones and carotenoids was investigated by comparing the incorporation of [14C]mevalonate into segments of different age from green and etiolated leaves of 22 C-grown rye seedlings (Secale cereale L.) and from 32 C-grown rye leaves which contained bleached and proplastid-like ribosome-deficient plastids, due to a heat-sensitivity of 70S ribosome formation. The contents of plastidic isoprenoids were much lower (between 2 - 30%) in the achlorophyllous than in green leaves. In green leaves [14C]mevalonate incorporation into non-polar lipids and into plastoquinone was partially inhibited in the presence of gabaculin, an inhibitor of chlorophyll synthesis. However, except for β-carotene, [14C]mevalonate incorporation into isoprenoids continuously increased with age also in achlorophyllous etiolated or 32 °C-grown, as in green, leaves and was, except for P-carotene and plastoquinone, higher in etiolated than in green leaves. In bleached °32 C-grown leaves [14C]mevalonate incorporation into all plastidic isoprenoids was strikingly (up to 45-fold) higher than in green control leaves. While degradation of P-carotene was greatly enhanced in bleached 32 °C-grown leaves, relative to green control leaves, and could thus compensate for a higher apparent synthesis, chase experiments did not reveal any marked differences of the turnover of other isoprenoids. The half times of plastoquinone. phylloquinone and lutein were in the order of 2-3 days. Within a 24 h chase period a-tocopherol degradation did not become apparent. Uptake of [14C]mevalonate and [14C]isopentenyl pyrophosphate by isolated bleached plastids from 32 °C-grown leaves was much more rapid than by chloroplasts and resulted in higher precursor accumulation within the organelle. While mevalonate incorporation into isoprenoid lipids was not detected, isopentenyl pyrophosphate was incorporated into isoprenoid lipids, including plastoquinone. Rates of incorporation by isolated chloroplasts or bleached plastids were of similar order. The results illustrate that divergent types of plastid differentiation are associated with fundamental developmental changes of the metabolic flow of isoprenoid precursors between different products and compartments and, in particular, with changes of import into the plastid compartment.
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Clomburg, James M., Shuai Qian, Zaigao Tan, Seokjung Cheong y Ramon Gonzalez. "The isoprenoid alcohol pathway, a synthetic route for isoprenoid biosynthesis". Proceedings of the National Academy of Sciences 116, n.º 26 (11 de junio de 2019): 12810–15. http://dx.doi.org/10.1073/pnas.1821004116.
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The more than 50,000 isoprenoids found in nature are all derived from the 5-carbon diphosphates isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP). Natively, IPP and DMAPP are generated by the mevalonate (MVA) and 2-C-methyl-d-erythritol-4-phosphate (MEP) pathways, which have been engineered to produce compounds with numerous applications. However, as these pathways are inherently constrained by carbon, energy inefficiencies, and their roles in native metabolism, engineering for isoprenoid biosynthesis at high flux, titer, and yield remains a challenge. To overcome these limitations, here we develop an alternative synthetic pathway termed the isoprenoid alcohol (IPA) pathway that centers around the synthesis and subsequent phosphorylation of IPAs. We first established a lower IPA pathway for the conversion of IPAs to isoprenoid pyrophosphate intermediates that enabled the production of greater than 2 g/L geraniol from prenol as well as limonene, farnesol, diaponeurosporene, and lycopene. We then designed upper IPA pathways for the generation of (iso)prenol from central carbon metabolites with the development of a route to prenol enabling its synthesis at more than 2 g/L. Using prenol as the linking intermediate further facilitated an integrated IPA pathway that resulted in the production of nearly 0.6 g/L total monoterpenoids from glycerol as the sole carbon source. The IPA pathway provides an alternative route to isoprenoids that is more energy efficient than native pathways and can serve as a platform for targeting a repertoire of isoprenoid compounds with application as high-value pharmaceuticals, commodity chemicals, and fuels.
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Díaz-Pérez, A. L., A. N. Zavala-Hernández, C. Cervantes y J. Campos-García. "The gnyRDBHAL Cluster Is Involved in Acyclic Isoprenoid Degradation in Pseudomonas aeruginosa". Applied and Environmental Microbiology 70, n.º 9 (septiembre de 2004): 5102–10. http://dx.doi.org/10.1128/aem.70.9.5102-5110.2004.
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ABSTRACT Pseudomonas aeruginosa PAO1 mutants affected in the ability to degrade acyclic isoprenoids were isolated with transposon mutagenesis. The gny cluster (for geranoyl), which encodes the enzymes involved in the lower pathway of acyclic isoprenoid degradation, was identified. The gny cluster is constituted by five probable structural genes, gnyDBHAL, and a possible regulatory gene, gnyR. Mutations in the gnyD, gnyB, gnyA, or gnyL gene caused inability to assimilate acyclic isoprenoids of the citronellol family of compounds. Transcriptional analysis showed that expression of the gnyB gene was induced by citronellol and repressed by glucose, whereas expression of the gnyR gene had the opposite behavior. Western blot analysis of citronellol-grown cultures showed induction of biotinylated proteins of 70 and 73 kDa, which probably correspond to 3-methylcrotonoyl-coenzyme A (CoA) carboxylase and geranoyl-CoA carboxylase (GCCase) alpha subunits, respectively. The 73-kDa biotinylated protein, identified as the α-GCCase subunit, is encoded by gnyA. Intermediary metabolites of the isoprenoid pathway, citronellic and geranic acids, were shown to accumulate in gnyB and gnyA mutants. Our data suggest that the protein products encoded in the gny cluster are the β and α subunits of geranoyl-CoA carboxylase (GnyB and GnyA), the citronelloyl-CoA dehydrogenase (GnyD), the γ-carboxygeranoyl-CoA hydratase (GnyH), and the 3-hydroxy-γ-carboxygeranoyl-CoA lyase (GnyL). We conclude that the gnyRDBHAL cluster is involved in isoprenoid catabolism.
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Fons, Françoise, Didier Froissard, Jean-Marie Bessière, Alain Fruchier, Bruno Buatois y Sylvie Rapior. "Volatile Composition of Six Horsetails: Prospects and Perspectives". Natural Product Communications 8, n.º 4 (abril de 2013): 1934578X1300800. http://dx.doi.org/10.1177/1934578x1300800426.
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Six horsetails were investigated for volatile organic compounds (VOC) by GC-MS using organic solvent extraction. Seventy-five VOC biosynthesized from the shikimic, lipidic and terpenic pathways including isoprenoid derivatives were detected from these putative natural resources. E. palustre var. americana contained mainly lipidic derivatives, i.e., 1-octen-3-ol (mushroom-like odor), ( E)-2-hexenoic acid (fruity odor) and ( E)-2-hexenal (green odor). Many isoprenoid flavour precursors, i.e., 3-oxo-α-ionol (spicy odor) and ( E, E)-pseudoionone (balsamic odor), as well as odorous benzenic derivatives, i.e, phenylethanal (hyacinth, lilac note) and 2-phenylethanol (rose odor) contributed to the odor of E. arvense. The volatile pattern of E. telmateia is dominated by high amounts of isoprenoids and benzenic derivatives. The complex volatile profiles of E. hyemale and E. ramosissimum are based on ferulic acid isomers, along with either ( E)-2-heptenal (green vegetable-like odor) or 4-vinylguaiacol (spicy clove smoky odor) for E. hyemale and E ramosissimum, respectively. The broad spectrum of E. scirpioides shows the lowest VOC content with high amount of isoprenoids (46.9%), mainly ionone derivatives. Equisetum resources are of great interest as bioactive litter and new potential functional feed ingredients.
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Howe, Ruth, Megan Kelly, John Jimah, Dana Hodge y Audrey R. Odom. "Isoprenoid Biosynthesis Inhibition Disrupts Rab5 Localization and Food Vacuolar Integrity in Plasmodium falciparum". Eukaryotic Cell 12, n.º 2 (7 de diciembre de 2012): 215–23. http://dx.doi.org/10.1128/ec.00073-12.
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ABSTRACT The antimalarial agent fosmidomycin is a validated inhibitor of the nonmevalonate isoprenoid biosynthesis (methylerythritol 4-phosphate [MEP]) pathway in the malaria parasite, Plasmodium falciparum . Since multiple classes of prenyltransferase inhibitors kill P. falciparum , we hypothesized that protein prenylation was one of the essential functions of this pathway. We found that MEP pathway inhibition with fosmidomycin reduces protein prenylation, confirming that de novo isoprenoid biosynthesis produces the isoprenyl substrates for protein prenylation. One important group of prenylated proteins is small GTPases, such as Rab family members, which mediate cellular vesicular trafficking. We have found that Rab5 proteins dramatically mislocalize upon fosmidomycin treatment, consistent with a loss of protein prenylation. Fosmidomycin treatment caused marked defects in food vacuolar morphology and integrity, consistent with a defect in Rab-mediated vesicular trafficking. These results provide insights to the biological functions of isoprenoids in malaria parasites and may assist the rational selection of secondary agents that will be useful in combination therapy with new isoprenoid biosynthesis inhibitors.
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Weivoda, Megan M. y Raymond J. Hohl. "Effects of Farnesyl Pyrophosphate Accumulation on Calvarial Osteoblast Differentiation". Endocrinology 152, n.º 8 (17 de mayo de 2011): 3113–22. http://dx.doi.org/10.1210/en.2011-0016.
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Statins, drugs commonly used to lower serum cholesterol, have been shown to stimulate osteoblast differentiation and bone formation. Statins inhibit 3-hydroxy-3-methylglutaryl (HMG)-coenzyme A reductase (HMGCR), the first step of the isoprenoid biosynthetic pathway, leading to the depletion of the isoprenoids farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP). The effects of statins on bone have previously been attributed to the depletion of GGPP, because the addition of exogenous GGPP prevented statin-stimulated osteoblast differentiation in vitro. However, in a recent report, we demonstrated that the specific depletion of GGPP did not stimulate but, in fact, inhibited osteoblast differentiation. This led us to hypothesize that isoprenoids upstream of GGPP play a role in the regulation of osteoblast differentiation. We demonstrate here that the expression of HMGCR and FPP synthase decreased during primary calvarial osteoblast differentiation, correlating with decreased FPP and GGPP levels during differentiation. Zaragozic acid (ZGA) inhibits the isoprenoid biosynthetic pathway enzyme squalene synthase, leading to an accumulation of the squalene synthase substrate FPP. ZGA treatment of calvarial osteoblasts led to a significant increase in intracellular FPP and resulted in inhibition of osteoblast differentiation as measured by osteoblastic gene expression, alkaline phosphatase activity, and matrix mineralization. Simultaneous HMGCR inhibition prevented the accumulation of FPP and restored osteoblast differentiation. In contrast, specifically inhibiting GGPPS to lower the ZGA-induced increase in GGPP did not restore osteoblast differentiation. The specificity of HMGCR inhibition to restore osteoblast differentiation of ZGA-treated cultures through the reduction in isoprenoid accumulation was confirmed with the addition of exogenous mevalonate. Similar to ZGA treatment, exogenous FPP inhibited the mineralization of primary calvarial osteoblasts. Interestingly, the effects of FPP accumulation on osteoblasts were found to be independent of protein farnesylation. Our findings are the first to demonstrate that the accumulation of FPP impairs osteoblast differentiation and suggests that the depletion of this isoprenoid may be necessary for normal and statin-induced bone formation.
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Poliquin, Kelly, Yuri V. Ershov, Francis X. Cunningham, Tinsay T. Woreta, R. Raymond Gantt y Elisabeth Gantt. "Inactivation of sll1556 in Synechocystis Strain PCC 6803 Impairs Isoprenoid Biosynthesis from Pentose Phosphate Cycle Substrates In Vitro". Journal of Bacteriology 186, n.º 14 (15 de julio de 2004): 4685–93. http://dx.doi.org/10.1128/jb.186.14.4685-4693.2004.
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ABSTRACT In cyanobacteria many compounds, including chlorophylls, carotenoids, and hopanoids, are synthesized from the isoprenoid precursors isopentenyl diphosphate (IPP) and dimethylallyl diphosphate. Isoprenoid biosynthesis in extracts of the cyanobacterium Synechocystis strain PCC 6803 grown under photosynthetic conditions, stimulated by pentose phosphate cycle substrates, does not appear to require methylerythritol phosphate pathway intermediates. The sll1556 gene, distantly related to type 2 IPP isomerase genes, was disrupted by insertion of a Kanr cassette. The mutant was fully viable under photosynthetic conditions although impaired in the utilization of pentose phosphate cycle substrates. Compared to the parental strain the Δsll1556 mutant (i) is deficient in isoprenoid biosynthesis in vitro with substrates including glyceraldehyde-3-phosphate, fructose-6-phosphate, and glucose-6-phosphate; (ii) has smaller cells (diameter ca. 13% less); (iii) has fewer thylakoids (ca. 30% less); and (iv) has a more extensive fibrous outer wall layer. Isoprenoid biosynthesis is restored with pentose phosphate cycle substrates plus the recombinant Sll1556 protein in the Δsll1556 supernatant fraction. IPP isomerase activity could not be demonstrated for the purified Sll1556 protein under our in vitro conditions. The reduction of thylakoid area and the effect on outer wall layer components are consistent with an impairment of isoprenoid biosynthesis in the mutant, possibly via hopanoid biosynthesis. Our findings are consistent with an alternate metabolic shunt for biosynthesis of isoprenoids.
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SCHWENDER, Jörg, Myriam SEEMANN, Hartmut K. LICHTENTHALER y Michel ROHMER. "Biosynthesis of isoprenoids (carotenoids, sterols, prenyl side-chains of chlorophylls and plastoquinone) via a novel pyruvate/glyceraldehyde 3-phosphate non-mevalonate pathway in the green alga Scenedesmus obliquus*". Biochemical Journal 316, n.º 1 (15 de mayo de 1996): 73–80. http://dx.doi.org/10.1042/bj3160073.
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Isoprenoid biosynthesis was investigated in the green alga Scenedesmus obliquus grown heterotrophically on 13C-labelled glucose and acetate. Several isoprenoid compounds were isolated and investigated by 13C-NMR spectroscopy. According to the 13C-labelling pattern indicated by the 13C-NMR spectra, the biosynthesis of all plastidic isoprenoids investigated (prenyl side-chains of chlorophylls and plastoquinone-9, and the carotenoids β-carotene and lutein), as well as of the non-plastidic cytoplasmic sterols, does not proceed via the classical acetate/mevalonate pathway (which leads from acetyl-CoA via mevalonate to isopentenyl diphosphate), but via the novel glyceraldehyde 3-phosphate/pyruvate route recently detected in eubacteria. Formation of isopentenyl diphosphate involves the condensation of a C2 unit derived from pyruvate decarboxylation with glyceraldehyde 3-phosphate and a transposition yielding the branched C5 skeleton of isoprenic units.
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Qidwai, Tabish, Farrukh Jamal, Mohd Y. Khan y Bechan Sharma. "Exploring Drug Targets in Isoprenoid Biosynthetic Pathway forPlasmodium falciparum". Biochemistry Research International 2014 (2014): 1–12. http://dx.doi.org/10.1155/2014/657189.
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Emergence of rapid drug resistance to existing antimalarial drugs inPlasmodium falciparumhas created the need for prediction of novel targets as well as leads derived from original molecules with improved activity against a validated drug target. The malaria parasite has a plant plastid-like apicoplast. To overcome the problem of falciparum malaria, the metabolic pathways in parasite apicoplast have been used as antimalarial drug targets. Among several pathways in apicoplast, isoprenoid biosynthesis is one of the important pathways for parasite as its multiplication in human erythrocytes requires isoprenoids. Therefore targeting this pathway and exploring leads with improved activity is a highly attractive approach. This report has explored progress towards the study of proteins and inhibitors of isoprenoid biosynthesis pathway. For more comprehensive analysis, antimalarial drug-protein interaction has been covered.
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Lombard, Jonathan, Purificación López-García y David Moreira. "Phylogenomic Investigation of Phospholipid Synthesis in Archaea". Archaea 2012 (2012): 1–13. http://dx.doi.org/10.1155/2012/630910.
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Archaea have idiosyncratic cell membranes usually based on phospholipids containing glycerol-1-phosphate linked by ether bonds to isoprenoid lateral chains. Since these phospholipids strongly differ from those of bacteria and eukaryotes, the origin of the archaeal membranes (and by extension, of all cellular membranes) was enigmatic and called for accurate evolutionary studies. In this paper we review some recent phylogenomic studies that have revealed a modified mevalonate pathway for the synthesis of isoprenoid precursors in archaea and suggested that this domain uses an atypical pathway of synthesis of fatty acids devoid of any acyl carrier protein, which is essential for this activity in bacteria and eukaryotes. In addition, we show new or updated phylogenetic analyses of enzymes likely responsible for the isoprenoid chain synthesis from their precursors and the phospholipid synthesis from glycerol phosphate, isoprenoids, and polar head groups. These results support that most of these enzymes can be traced back to the last archaeal common ancestor and, in many cases, even to the last common ancestor of all living organisms.
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Dunn, Shannon E., Sawsan Youssef, Matthew J. Goldstein, Thomas Prod'homme, Martin S. Weber, Scott S. Zamvil y Lawrence Steinman. "Isoprenoids determine Th1/Th2 fate in pathogenic T cells, providing a mechanism of modulation of autoimmunity by atorvastatin". Journal of Experimental Medicine 203, n.º 2 (13 de febrero de 2006): 401–12. http://dx.doi.org/10.1084/jem.20051129.
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3-hydroxy-3-methylglutaryl–coenzyme A (HMG-CoA) reductase is a critical enzyme in the mevalonate pathway that regulates the biosynthesis of cholesterol as well as isoprenoids that mediate the membrane association of certain GTPases. Blockade of this enzyme by atorvastatin (AT) inhibits the destructive proinflammatory T helper cell (Th)1 response during experimental autoimmune encephalomyelitis and may be beneficial in the treatment of multiple sclerosis and other Th1-mediated autoimmune diseases. Here we present evidence linking specific isoprenoid intermediates of the mevalonate pathway to signaling pathways that regulate T cell autoimmunity. We demonstrate that the isoprenoid geranylgeranyl-pyrophosphate (GGPP) mediates proliferation, whereas both GGPP and its precursor, farnesyl-PP, regulate the Th1 differentiation of myelin-reactive T cells. Depletion of these isoprenoid intermediates in vivo via oral AT administration hindered these T cell responses by decreasing geranylgeranylated RhoA and farnesylated Ras at the plasma membrane. This was associated with reduced extracellular signal–regulated kinase (ERK) and p38 phosphorylation and DNA binding of their cotarget c-fos in response to T cell receptor activation. Inhibition of ERK and p38 mimicked the effects of AT and induced a Th2 cytokine shift. Thus, by connecting isoprenoid availability to regulation of Th1/Th2 fate, we have elucidated a mechanism by which AT may suppress Th1-mediated central nervous system autoimmune disease.
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Onono, Fredrick, Thangaiah Subramanian, Manjula Sunkara, Karunai Leela Subramanian, H. Peter Spielmann y Andrew J. Morris. "Efficient Use of Exogenous Isoprenols for Protein Isoprenylation by MDA-MB-231 Cells Is Regulated Independently of the Mevalonate Pathway". Journal of Biological Chemistry 288, n.º 38 (1 de agosto de 2013): 27444–55. http://dx.doi.org/10.1074/jbc.m113.482307.
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Mammalian cells can use exogenous isoprenols to generate isoprenoid diphosphate substrates for protein isoprenylation, but the mechanism, efficiency, and biological importance of this process are not known. We developed mass spectrometry-based methods using chemical probes and newly synthesized stable isotope-labeled tracers to quantitate incorporation of exogenously provided farnesol, geranylgeraniol, and unnatural analogs of these isoprenols containing an aniline group into isoprenoid diphosphates and protein isoprenylcysteines by cultured human cancer cell lines. We found that at exogenous isoprenol concentrations >10 μm, this process can generate as much as 50% of the cellular isoprenoid diphosphate pool used for protein isoprenylation. Mutational activation of p53 in MDA-MB-231 breast cancer cells up-regulates the mevalonate pathway to promote tumor invasiveness. p53 silencing or pharmacological inhibition of HMG-CoA reductase in these cells decreases protein isoprenylation from endogenously synthesized isoprenoids but enhances the use of exogenous isoprenols for this purpose, indicating that this latter process is regulated independently of the mevalonate pathway. Our observations suggest unique opportunities for design of cancer cell-directed therapies and may provide insights into mechanisms underlying pleiotropic therapeutic benefits and unwanted side effects of mevalonate pathway inhibition.
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Devi, Kamalakshi, Lochana Patar, Mahendra K. Modi y Priyabrata Sen. "An Insight Into Structure, Function, and Expression Analysis of 3-Hydroxy-3-Methylglutaryl-CoA Reductase of Cymbopogon winterianus". Bioinformatics and Biology Insights 11 (1 de enero de 2017): 117793221770173. http://dx.doi.org/10.1177/1177932217701735.
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Citronella ( Cymbopogon winterianus) is one of the richest sources of high-value isoprenoid aromatic compounds used as flavour, fragrance, and therapeutic elements. These isoprenoid compounds are synthesized by 2 independent pathways: mevalonate pathway and 2-C-methyl-d-erythritol-4-phosphate pathway. Evidence suggests that 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) is a rate-controlling enzyme for the synthesis of variety of isoprenoids. This study reports the isolation, characterization, and tissue-specific expression analysis of HMGR from citronella. The modelled HMGR is a class I type of HMGR enzyme with 3-domain architecture. The active site comprises a cofactor (nicotinamide adenine dinucleotide phosphate) and the substrate-binding motifs. The real-time and quantitative reverse transcription-polymerase chain reaction results revealed equal expression level in both leaf sheath and root tissue. The results from our study shall be a valuable resource for future molecular intervention to alter the metabolic flux towards improvement of key active ingredient in this important medicinal plant.
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Dimster-Denk, D., M. K. Thorsness y J. Rine. "Feedback regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase in Saccharomyces cerevisiae." Molecular Biology of the Cell 5, n.º 6 (junio de 1994): 655–65. http://dx.doi.org/10.1091/mbc.5.6.655.
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In eukaryotic cells all isoprenoids are synthesized from a common precursor, mevalonate. The formation of mevalonate from 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) is catalyzed by HMG-CoA reductase and is the first committed step in isoprenoid biosynthesis. In mammalian cells, synthesis of HMG-CoA reductase is subject to feedback regulation at multiple molecular levels. We examined the state of feedback regulation of the synthesis of the HMG-CoA reductase isozyme encoded by the yeast gene HMG1 to examine the generality of this regulatory pattern. In yeast, synthesis of Hmg1p was subject to feedback regulation. This regulation of HMG-CoA reductase synthesis was independent of any change in the level of HMG1 mRNA. Furthermore, regulation of Hmg1p synthesis was keyed to the level of a nonsterol product of the mevalonate pathway. Manipulations of endogenous levels of several isoprenoid intermediates, either pharmacologically or genetically, suggested that mevalonate levels may control the synthesis of Hmg1p through effects on translation.
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Niu, Fu-Xing, Qian Lu, Yi-Fan Bu y Jian-Zhong Liu. "Metabolic engineering for the microbial production of isoprenoids: Carotenoids and isoprenoid-based biofuels". Synthetic and Systems Biotechnology 2, n.º 3 (septiembre de 2017): 167–75. http://dx.doi.org/10.1016/j.synbio.2017.08.001.
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Wiley, Jessica D., Emilio F. Merino, Priscilla M. Krai, Kyle J. McLean, Abhai K. Tripathi, Joel Vega-Rodríguez, Marcelo Jacobs-Lorena, Michael Klemba y Maria B. Cassera. "Isoprenoid Precursor Biosynthesis Is the Essential Metabolic Role of the Apicoplast during Gametocytogenesis in Plasmodium falciparum". Eukaryotic Cell 14, n.º 2 (1 de diciembre de 2014): 128–39. http://dx.doi.org/10.1128/ec.00198-14.
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ABSTRACT The malaria parasite harbors a relict plastid called the apicoplast and its discovery opened a new avenue for drug discovery and development due to its unusual, nonmammalian metabolism. The apicoplast is essential during the asexual intraerythrocytic and hepatic stages of the parasite, and there is strong evidence supporting its essential metabolic role during the mosquito stages of the parasite. Supply of the isoprenoid building blocks isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) is the essential metabolic function of the apicoplast during the asexual intraerythrocytic stages. However, the metabolic role of the apicoplast during gametocyte development, the malaria stages transmitted to the mosquito, remains unknown. In this study, we showed that production of IPP for isoprenoid biosynthesis is the essential metabolic function of the apicoplast during gametocytogenesis, by obtaining normal gametocytes lacking the apicoplast when supplemented with IPP. When IPP supplementation was removed early in gametocytogenesis, developmental defects were observed, supporting the essential role of isoprenoids for normal gametocytogenesis. Furthermore, mosquitoes infected with gametocytes lacking the apicoplast developed fewer and smaller oocysts that failed to produce sporozoites. This finding further supports the essential role of the apicoplast in establishing a successful infection in the mosquito vector. Our study supports isoprenoid biosynthesis as a valid drug target for development of malaria transmission-blocking inhibitors.
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Kurup, Ravi Kumar y Parameswara Achutha Kurup. "Hypothalamic digoxin-mediated model for epileptogenesis". Acta Neuropsychiatrica 15, n.º 3 (junio de 2003): 115–21. http://dx.doi.org/10.1034/j.1601-5215.2003.00020.x.
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Background/aims:This study assessed the changes in the isoprenoid pathway and its metabolites in seizure disorder (ILAE classification – I generalized – idiopathic generalized epilepsy with age-related onset – epilepsy with generalized tonic clonic seizures on awakening) and the metabolic cascade produced by isoprenoid pathway dysregulation.Methods:The following parameters were assessed in seizure disorder: isoprenoid pathway metabolites, tyrosine and tryptophan catabolites, glycoconjugates metabolism and red blood cell (RBC) membrane composition.Results:There was elevation in plasma HMG-CoA reductase activity, serum digoxin and dolichol and a reduction in RBC membrane Na-K+ATPase activity, serum magnesium and ubiquinone levels. Serum tryptophan, serotonin, strychnine, nicotine and quinolinic acid were elevated while tyrosine, dopamine, morphine and norepinephrine were decreased. The total serum glycosaminoglycans and glycosaminoglycan fractions (except dermatan sulfate), the activity of glycosaminoglycans (GAG) degrading enzymes and glycohydrolases, carbohydrate residues of glycoproteins and serum glycolipids were elevated. Total serum cholesterol, LDL cholesterol and free fatty acids were increased while HDL cholesterol and triglycerides were unaltered. The concentration of membrane hexose, fucose, cholesterol and phospholipids in the RBC membrane decreased significantly but the total RBC membrane GAG was unaltered.Conclusions:Epileptogenesis could be due to a dysfunctional isoprenoidal pathway and paroxysmal hypothalamic digoxin hypersecretion.
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Alves, E. G., K. Jardine, J. Tota, A. Jardine, A. M. Yáñez-Serrano, T. Karl, J. Tavares et al. "Seasonality of isoprenoid emissions from a primary rainforest in central Amazonia". Atmospheric Chemistry and Physics Discussions 15, n.º 20 (26 de octubre de 2015): 28867–913. http://dx.doi.org/10.5194/acpd-15-28867-2015.
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Abstract. Tropical rainforests are an important source of isoprenoid and other Volatile Organic Compound (VOC) emissions to the atmosphere. The seasonal variation of these compounds is however still poorly understood. In this study, profiles were collected of the vertical profile of mixing ratios of isoprene, total monoterpenes and total sesquiterpenes, within and above the canopy, in a primary rainforest in central Amazonia, using a Proton Transfer Reaction-Mass Spectrometer (PTR-MS). Fluxes of these compounds from the canopy into the atmosphere were estimated from PTR-MS measurements by using an inverse Lagrangian transport model. Measurements were carried out continuously from September 2010 to January 2011, encompassing the dry and wet seasons. Mixing ratios were higher during the dry (isoprene – 2.68 ± 0.9 ppbv, total monoterpenes – 0.67 ± 0.3 ppbv; total sesquiterpenes – 0.09 ± 0.07 ppbv) than the wet season (isoprene – 1.66 ± 0.9 ppbv, total monoterpenes – 0.47 ± 0.2 ppbv; total sesquiterpenes – 0.03 ± 0.02 ppbv) for all compounds. Ambient air temperature and photosynthetically active radiation (PAR) behaved similarly. Daytime isoprene and total monoterpene mixing ratios were highest within the canopy, rather than near the ground or above the canopy. By comparison, daytime total sesquiterpene mixing ratios were highest near the ground. Daytime fluxes varied significantly between seasons for all compounds. The maximums for isoprene (2.53 ± 0.5 μmol m−2 h−1) and total monoterpenes (1.77 ± 0.05 μmol m−2 h−1) were observed in the late dry season, whereas the maximum for total sesquiterpenes was found during the dry-to-wet transition season (0.77 ± 0.1 μmol m−2 h−1). These flux estimates suggest that the canopy is the main source of isoprenoids to the atmosphere for all seasons. However, uncertainties in turbulence parameterization near the ground could affect estimates of fluxes that come from the ground. Leaf phenology seemed to be an important driver of seasonal variation of isoprenoid emissions. Although remote sensing observations of changes in leaf area index were used to estimate leaf phenology, MEGAN 2.1 did not fully capture the behavior of seasonal emissions observed in this study. This could be a result of very local effects on the observed emissions, but also suggest that other parameters need to be better determined in Biogenic Volatile Organic Compound (BVOC) models. Our results support established findings that seasonality of isoprenoids are driven by seasonal changes in light, temperature and leaf phenology. However, they suggest that leaf phenology and its role on isoprenoid production and emission from tropical plant species needs to be better understood in order to develop mechanistic explanations for seasonal variation in emissions. This also may reduce the uncertainties of model estimates associated with the responses to environmental factors. Therefore, this study strongly encourages long-term measurements of isoprenoid emissions, environmental factors and leaf phenology from leaf to ecosystem scale, with the purpose of improving BVOC model approaches that can characterize seasonality of isoprenoid emissions from tropical rainforests.
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Alves, Eliane G., Kolby Jardine, Julio Tota, Angela Jardine, Ana Maria Yãnez-Serrano, Thomas Karl, Julia Tavares et al. "Seasonality of isoprenoid emissions from a primary rainforest in central Amazonia". Atmospheric Chemistry and Physics 16, n.º 6 (23 de marzo de 2016): 3903–25. http://dx.doi.org/10.5194/acp-16-3903-2016.
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Abstract. Tropical rainforests are an important source of isoprenoid and other volatile organic compound (VOC) emissions to the atmosphere. The seasonal variation of these compounds is however still poorly understood. In this study, vertical profiles of mixing ratios of isoprene, total monoterpenes and total sesquiterpenes, were measured within and above the canopy, in a primary rainforest in central Amazonia, using a proton transfer reaction – mass spectrometer (PTR-MS). Fluxes of these compounds from the canopy into the atmosphere were estimated from PTR-MS measurements by using an inverse Lagrangian transport model. Measurements were carried out continuously from September 2010 to January 2011, encompassing the dry and wet seasons. Mixing ratios were higher during the dry (isoprene – 2.68 ± 0.9 ppbv, total monoterpenes – 0.67 ± 0.3 ppbv; total sesquiterpenes – 0.09 ± 0.07 ppbv) than the wet season (isoprene – 1.66 ± 0.9 ppbv, total monoterpenes – 0.47 ± 0.2 ppbv; total sesquiterpenes – 0.03 ± 0.02 ppbv) for all compounds. Ambient air temperature and photosynthetically active radiation (PAR) behaved similarly. Daytime isoprene and total monoterpene mixing ratios were highest within the canopy, rather than near the ground or above the canopy. By comparison, daytime total sesquiterpene mixing ratios were highest near the ground. Daytime fluxes varied significantly between seasons for all compounds. The maximums for isoprene (2.53 ± 0.5 µmol m−2 h−1) and total monoterpenes (1.77 ± 0.05 µmol m−2 h−1) were observed in the late dry season, whereas the maximum for total sesquiterpenes was found during the dry-to-wet transition season (0.77 ± 0.1 µmol m−2 h−1). These flux estimates suggest that the canopy is the main source of isoprenoids emitted into the atmosphere for all seasons. However, uncertainties in turbulence parameterization near the ground could affect estimates of fluxes that come from the ground. Leaf phenology seemed to be an important driver of seasonal variation of isoprenoid emissions. Although remote sensing observations of changes in leaf area index were used to estimate leaf phenology, MEGAN 2.1 did not fully capture the behavior of seasonal emissions observed in this study. This could be a result of very local effects on the observed emissions, but also suggest that other parameters need to be better determined in biogenic volatile organic compound (BVOC) models. Our results support established findings that seasonality of isoprenoids are driven by seasonal changes in light, temperature and leaf phenology. However, they suggest that leaf phenology and its role on isoprenoid production and emission from tropical plant species needs to be better understood in order to develop mechanistic explanations for seasonal variation in emissions. This also may reduce the uncertainties of model estimates associated with the responses to environmental factors. Therefore, this study strongly encourages long-term measurements of isoprenoid emissions, environmental factors and leaf phenology from leaf to ecosystem scale, with the purpose of improving BVOC model approaches that can characterize seasonality of isoprenoid emissions from tropical rainforests.
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Bertamini, Massimo, Maria Stella Grando, Pietro Zocca, Michele Pedrotti, Silvia Lorenzi y Luca Cappellin. "Linking monoterpenes and abiotic stress resistance in grapevines". BIO Web of Conferences 13 (2019): 01003. http://dx.doi.org/10.1051/bioconf/20191301003.
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Rising temperatures and ozone levels are among the most striking stressful phenomena of global climate changes, and they threaten plants that are unable to react rapidly and efficiently. Generic responses of plants to stresses include the production of excess reactive oxygen species (ROS). Excessive ROS accumulation can lead to extensive oxidation of important components such as nucleic acids, proteins and lipids which can further exacerbate ROS accumulation leading to programmed cell death. Although most studies on plant antioxidants have focused on non-volatile compounds, volatiles belonging to the isoprenoid family have been implicated in the protection against abiotic stresses, in particular thermal and oxidative stress whose frequency and extent is being exacerbated by ongoing global change and anthropogenic pollution. Historically, research has focused on isoprene, demonstrating that isoprene-emitting plants are more tolerant to ozone exposure and heat stress, reducing ROS accumulation. Yet, evidence is being compiled that shows other volatile isoprenoids may be involved in plant responses against abiotic stresses. Grapevines are not isoprene emitters but some varieties produce other volatile isoprenoids such as monoterpenes. We investigated photosynthesis and emission of volatile organic compounds upon heat stress in two Vitis vinifera cv. ‘Chardonnay’ clones differing only for a mutation in the DXS gene (2-C-methyl-D-erythritol 4-phosphate (MEP) pathway), regulating volatile isoprenoid biosynthesis. We showed that the mutation led to a strong increase in monoterpene emission upon heat stress. At the same time, maximum photochemical quantum yield (Fv/Fm ratio) of PSII was affected by the stress in the non-emitting clone while the monoterpene emitter showed a significant resilience, thus indicating a possible antioxidant role of monoterpenes in grapevine. Future mechanistic studies should focus on unveiling the actual mechanism responsible for such findings.
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Lachowicz-Wiśniewska, Sabina, Ireneusz Kapusta, Carla M. Stinco, Antonio J. Meléndez-Martínez, Anna Bieniek, Ireneusz Ochmian y Zygmunt Gil. "Distribution of Polyphenolic and Isoprenoid Compounds and Biological Activity Differences between in the Fruit Skin + Pulp, Seeds, and Leaves of New Biotypes of Elaeagnusmultiflora Thunb". Antioxidants 10, n.º 6 (26 de mayo de 2021): 849. http://dx.doi.org/10.3390/antiox10060849.
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The purpose of this study was to determine the distribution of polyphenolic and isoprenoid compounds and organic acids in the fruit skin + pulp, seeds, and leaves of six new biotypes of Elaeagnus multiflora Thunb., as well as their in vitro biological potency. The polyphenols and isoprenoids were determined with UPLC-PDA-MS/MS (ultra-performance liquid chromatography coupled to photodiode array detection and electrospray ionization tandem mass spectrometry) and RRLC-MS/MS (rapid resolution liquid chromatography/tandem mass spectrometry) methods, the organic acid with HPLC-RID (high-performance liquid chromatography coupled to a Refractive Index Detector), and the antioxidant capacity using ABTS and FRAP assays. Enzymatic activity was established as the ability to inhibit α-amylase, α-glucosidase, and pancreatic lipase. Owing to such an effective technique, 88 compounds were recorded, with 17 polyphenolic compounds and 3 isoprenoids identified for the first time in the seeds and leaves of cherry silverberry. In total, 55 compounds were identified in the leaves, 36 in the seeds, and 31 in the fruit skin + pulp. The predominant polyphenol was polymeric procyanidin (66–95% of total polyphenolics), whereas the predominant isoprenoids were chlorophyll b and (all-E)-lycopene. The results of our work noted that there are significant differences in the profiles of several secondary metabolites between the analyzed parts of the plant, and depending on the need, the compounds can be used to develop different innovative food or cosmetic products.
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Altincicek, Boran, Ann-Kristin Kollas, Silke Sanderbrand, Jochen Wiesner, Martin Hintz, Ewald Beck y Hassan Jomaa. "GcpE Is Involved in the 2-C-Methyl-d-Erythritol 4-Phosphate Pathway of Isoprenoid Biosynthesis in Escherichia coli". Journal of Bacteriology 183, n.º 8 (15 de abril de 2001): 2411–16. http://dx.doi.org/10.1128/jb.183.8.2411-2416.2001.
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ABSTRACT In a variety of organisms, including plants and several eubacteria, isoprenoids are synthesized by the mevalonate-independent 2-C-methyl-d-erythritol 4-phosphate (MEP) pathway. Although different enzymes of this pathway have been described, the terminal biosynthetic steps of the MEP pathway have not been fully elucidated. In this work, we demonstrate that thegcpE gene of Escherichia coli is involved in this pathway. E. coli cells were genetically engineered to utilize exogenously provided mevalonate for isoprenoid biosynthesis by the mevalonate pathway. These cells were then deleted for the essential gcpE gene and were viable only if the medium was supplemented with mevalonate or the cells were complemented with an episomal copy of gcpE.
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Mussoni, Luciana, Cristina Banfi, Luigi Sironi, Magda Arpaia y Elena Tremoli. "Fluvastatin Inhibits Basal and Stimulated Plasminogen Activator Inhibitor 1, but Induces Tissue Type Plasminogen Activator in Cultured Human Endothelial Cells". Thrombosis and Haemostasis 84, n.º 07 (2000): 59–64. http://dx.doi.org/10.1055/s-0037-1613968.
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SummaryThe effects of fluvastatin, a synthetic hydroxymethylglutaryl coenzyme A (HMG-CoA) inhibitor, on the biosynthesis of tissue plasminogen activator (t-PA) and of its major physiological inhibitor (plasminogen activator inhibitor type 1, PAI-1) were investigated in cultured human umbilical vein endothelial cells (HUVEC). Fluvastatin (0.1 to 2.5 µM), concentration-dependently reduced the release of PAI-1 antigen by unstimulated HUVEC, subsequent to a reduction in PAI-1 steady-state mRNA levels and de novo protein synthesis. In contrast, it increased t-PA secretion.The drug also reduced PAI-1 antigen secreted in response to 10 µg/ml bacterial lipopolysaccharide (LPS), 100 U/ml tumour necrosis factor α (TNFα) or 0.1 µM phorbol myristate acetate (PMA).Mevalonate (100 µM), a precursor of isoprenoids, added to cells simultaneously with fluvastatin, suppressed the effect of the drug on PAI-1 both in unstimulated and stimulated cells as well as on t-PA antigen. Among intermediates of the isoprenoid pathway, all-trans-geranylgeraniol (5 µM) but not farnesol (10 µM) prevented the effect of 2.5 µM fluvastatin on PAI-1 antigen, which suggests that the former intermediate of the isoprenoid synthesis is responsible for the observed effects.
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Qian, Jieying, Yong Liu, Chengtong Ma, Naixia Chao, Qicong Chen, Yangmei Zhang, Yu Luo, Danzhao Cai y Yaosheng Wu. "Positive Selection of Squalene Synthase in Cucurbitaceae Plants". International Journal of Genomics 2019 (9 de mayo de 2019): 1–15. http://dx.doi.org/10.1155/2019/5913491.
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Triterpenoid saponins are secondary metabolites synthesized through isoprenoid pathways in plants. Cucurbitaceae represent an important plant family in which many species contain cucurbitacins as secondary metabolites synthesized through isoprenoid and triterpenoid pathways. Squalene synthase (SQS) is required for the biosynthesis of isoprenoids, but the forces driving the evolution of SQS remain undetermined. In this study, 10 SQS cDNA sequences cloned from 10 species of Cucurbitaceae and 49 sequences of SQS downloaded from GenBank and UniProt databases were analyzed in a phylogenetic framework to identify the evolutionary forces for functional divergence. Through phylogenetic construction and positive selection analysis, we found that SQS sequences are under positive selection. The sites of positive selection map to functional and transmembrane domains. 180L, 189S, 194S, 196S, 265I, 289P, 389P, 390T, 407S, 408A, 410R, and 414N were identified as sites of positive selection that are important during terpenoid synthesis and map to transmembrane domains. 196S and 407S are phosphorylated and influence SQS catalysis and triterpenoid accumulation. These results reveal that positive selection is an important evolutionary force for SQS in plants. This provides new information into the molecular evolution of SQS within the Cucurbitaceae family.
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王, 秋军. "Recent Research on Isoprenoid Biosynthetic Pathway and Metabolic Regulation of Functional Isoprenoids in Medicinal Plants". Botanical Research 01, n.º 02 (2012): 23–29. http://dx.doi.org/10.12677/br.2012.12004.
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Fedor, Justin G., Andrew J. Y. Jones, Andrea Di Luca, Ville R. I. Kaila y Judy Hirst. "Correlating kinetic and structural data on ubiquinone binding and reduction by respiratory complex I". Proceedings of the National Academy of Sciences 114, n.º 48 (13 de noviembre de 2017): 12737–42. http://dx.doi.org/10.1073/pnas.1714074114.
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Respiratory complex I (NADH:ubiquinone oxidoreductase), one of the largest membrane-bound enzymes in mammalian cells, powers ATP synthesis by using the energy from electron transfer from NADH to ubiquinone-10 to drive protons across the energy-transducing mitochondrial inner membrane. Ubiquinone-10 is extremely hydrophobic, but in complex I the binding site for its redox-active quinone headgroup is ∼20 Å above the membrane surface. Structural data suggest it accesses the site by a narrow channel, long enough to accommodate almost all of its ∼50-Å isoprenoid chain. However, how ubiquinone/ubiquinol exchange occurs on catalytically relevant timescales, and whether binding/dissociation events are involved in coupling electron transfer to proton translocation, are unknown. Here, we use proteoliposomes containing complex I, together with a quinol oxidase, to determine the kinetics of complex I catalysis with ubiquinones of varying isoprenoid chain length, from 1 to 10 units. We interpret our results using structural data, which show the hydrophobic channel is interrupted by a highly charged region at isoprenoids 4–7. We demonstrate that ubiquinol-10 dissociation is not rate determining and deduce that ubiquinone-10 has both the highest binding affinity and the fastest binding rate. We propose that the charged region and chain directionality assist product dissociation, and that isoprenoid stepping ensures short transit times. These properties of the channel do not benefit the exhange of short-chain quinones, for which product dissociation may become rate limiting. Thus, we discuss how the long channel does not hinder catalysis under physiological conditions and the possible roles of ubiquinone/ubiquinol binding/dissociation in energy conversion.
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Giriwono, Puspo E., Hitoshi Shirakawa, Yusuke Ohsaki, Shoko Sato, Yukihide Aoyama, Hsin-Jung Ho, Tomoko Goto y Michio Komai. "Geranylgeraniol Suppresses the Expression of IRAK1 and TRAF6 to Inhibit NFκB Activation in Lipopolysaccharide-Induced Inflammatory Responses in Human Macrophage-Like Cells". International Journal of Molecular Sciences 20, n.º 9 (10 de mayo de 2019): 2320. http://dx.doi.org/10.3390/ijms20092320.
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Geranylgeraniol (GGOH), a natural isoprenoid found in plants, has anti-inflammatory effects via inhibiting the activation of nuclear factor-kappa B (NFκB). However, its detailed mechanism has not yet been elucidated. Recent studies have revealed that isoprenoids can modulate signaling molecules in innate immune responses. We found that GGOH decreased the expression of lipopolysaccharide (LPS)-induced inflammatory genes in human macrophage-like THP-1 cells. Furthermore, we observed that the suppression of NFκB signaling proteins, in particular interleukin-1 receptor-associated kinase 1 (IRAK1) and tumor necrosis factor receptor-associated factor 6 (TRAF6), occurred in GGOH-treated cells prior to LPS stimulation, suggesting an immunomodulatory effect. These results indicate that GGOH may modulate and help prevent excessive NFκB activation that can lead to numerous diseases.
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Dawson, D., K. Grice y R. Alexander. "STABLE HYDROGEN ISOTOPE RATIOS OF SEDIMENTARY HYDROCARBONS: A POTENTIAL METHOD FOR ASSESSING THERMAL MATURITY?" APPEA Journal 45, n.º 1 (2005): 253. http://dx.doi.org/10.1071/aj04022.
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A relationship has been identified between the maturity level of source rocks and the stable hydrogen isotopic compositions (δD) of extracted saturated hydrocarbons, based on the analysis of nine sediments and five crude oils from the Perth Basin (WA). The sediments cover the immature to late mature range. Distinct δD signatures are observed for the immature sediments where pristane and phytane are significantly depleted in deuterium (D) relative to the n-alkanes. With increasing maturity the difference between the δD values of n-alkanes and isoprenoids reduces as pristane and phytane become progressively enriched in D. The n-alkane–isoprenoid δD signature of the crude oils, including one from a different source facies, is similar to mature–late mature sediments representative of the peak oil–generative window. Enrichment of D in isoprenoids is attributed to isotopic exchange associated with thermal maturation. Average δD values of pristane and phytane correlate well with vitrinite reflectance, as does the biomarker maturity parameter Ts/Tm. The limited data set suggests that δD values of aliphatic hydrocarbons may be useful for establishing thermal maturity, particularly when other maturity parameters are not appropriate. Furthermore, we suggest δD values may be useful over a wider maturity range than traditional parameters, particularly at very high maturity where biomarker parameters are no longer effective.
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Zúñiga-Hertz, Juan P., Eduardo Rebelato, Adam Kassan, Abdelrahman M. Khalifa, Sameh S. Ali, Hemal H. Patel y Fernando Abdulkader. "Distinct pathways of cholesterol biosynthesis impact on insulin secretion". Journal of Endocrinology 224, n.º 1 (28 de octubre de 2014): 75–84. http://dx.doi.org/10.1530/joe-14-0348.
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Results from previous investigations have indicated that glucose-stimulated insulin secretion (GSIS) is affected by changes in cholesterol and its intermediates, but the precise link between secretion and cholesterol has not been thoroughly investigated. In this study, we show the contribution of both protein isoprenylation and cholesterol-dependent plasma membrane structural integrity to insulin secretion in INS-1E cells and mouse islets. Acute (2 h) inhibition of hydroxyl-methylglutaryl-CoA reductase by simvastatin (SIM) resulted in inhibition of GSIS without reduction in total cellular cholesterol content. This effect was prevented by cell loading with the isoprenyl molecule geranylgeranyl pyrophosphate. Chronic (24 h) inhibition of cholesterol biosynthesis resulted in inhibition of GSIS with a significant reduction in total cellular cholesterol content, which was also observed after the inhibition of cholesterol biosynthesis downstream of isoprenoid formation. Electron paramagnetic resonance analyses of INS-1E cells showed that the SIM-induced reduction in cholesterol increased plasma membrane fluidity. Thus, the blockade of cholesterol biosynthesis resulted in the reduction of availability of isoprenoids, followed by a reduction in the total cholesterol content associated with an increase in plasma membrane fluidity. Herein, we show the different contributions of cholesterol biosynthesis to GSIS, and propose that isoprenoid molecules and cholesterol-dependent signaling are dual regulators of proper β-cell function.
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KAJIWARA, Susumu, Paul D. FRASER, Keiji KONDO y Norihiko MISAWA. "Expression of an exogenous isopentenyl diphosphate isomerase gene enhances isoprenoid biosynthesis in Escherichia coli". Biochemical Journal 324, n.º 2 (1 de junio de 1997): 421–26. http://dx.doi.org/10.1042/bj3240421.
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Escherichia coli expressing the Erwinia carotenoid biosynthesis genes, crtE, crtB, crtI and crtY, form yellow-coloured colonies due to the presence of β-carotene. This host was used as a visible marker for evaluating regulatory systems operating in isoprenoid biosynthesis of E. coli. cDNAs enhancing carotenoid levels were isolated from the yeast Phaffia rhodozyma and the green alga Haematococcus pluvialis. Nucleotide sequence analysis indicated that they coded for proteins similar to isopentenyl diphosphate (IPP) isomerase of the yeast Saccharomyces cerevisiae. Determination of enzymic activity confirmed the identity of the gene products as IPP isomerases. The corresponding gene was isolated from the genomic library of S. cerevisiae based on its nucleotide sequence, and was confirmed to have the same effect as the above two IPP isomerase genes when introduced into the E. coli transformant accumulating β-carotene. In the three E. coli strains carrying the individual exogenous IPP isomerase genes, the increases in carotenoid levels are comparable to the increases in IPP isomerase enzyme activity with reference to control strains possessing the endogenous gene alone. These results imply that IPP isomerase forms an influential step in isoprenoid biosynthesis of the prokaryote E. coli, with potential for the efficient production of industrially useful isoprenoids by metabolic engineering.
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Mäki, Mari, Jussi Heinonsalo, Heidi Hellén y Jaana Bäck. "Contribution of understorey vegetation and soil processes to boreal forest isoprenoid exchange". Biogeosciences 14, n.º 5 (8 de marzo de 2017): 1055–73. http://dx.doi.org/10.5194/bg-14-1055-2017.
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Abstract. Boreal forest floor emits biogenic volatile organic compounds (BVOCs) from the understorey vegetation and the heterogeneous soil matrix, where the interactions of soil organisms and soil chemistry are complex. Earlier studies have focused on determining the net exchange of VOCs from the forest floor. This study goes one step further, with the aim of separately determining whether the photosynthesized carbon allocation to soil affects the isoprenoid production by different soil organisms, i.e., decomposers, mycorrhizal fungi, and roots. In each treatment, photosynthesized carbon allocation through roots for decomposers and mycorrhizal fungi was controlled by either preventing root ingrowth (50 µm mesh size) or the ingrowth of roots and fungi (1 µm mesh) into the soil volume, which is called the trenching approach. Isoprenoid fluxes were measured using dynamic (steady-state flow-through) chambers from the different treatments. This study aimed to analyze how important the understorey vegetation is as a VOC sink. Finally, a statistical model was constructed based on prevailing temperature, seasonality, trenching treatments, understory vegetation cover, above canopy photosynthetically active radiation (PAR), soil water content, and soil temperature to estimate isoprenoid fluxes. The final model included parameters with a statistically significant effect on the isoprenoid fluxes. The results show that the boreal forest floor emits monoterpenes, sesquiterpenes, and isoprene. Monoterpenes were the most common group of emitted isoprenoids, and the average flux from the non-trenched forest floor was 23 µg m−2 h−1. The results also show that different biological factors, including litterfall, carbon availability, biological activity in the soil, and physico-chemical processes, such as volatilization and absorption to the surfaces, are important at various times of the year. This study also discovered that understorey vegetation is a strong sink of monoterpenes. The statistical model, based on prevailing temperature, seasonality, vegetation effect, and the interaction of these parameters, explained 43 % of the monoterpene fluxes, and 34–46 % of individual α-pinene, camphene, β-pinene, and Δ3-carene fluxes.
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Ariyawutthiphan, Orapin, Toyoyuki Ose, Atsushi Minami, Sandip Sinde, Muneya Tsuda, Yong-Gui Gao, Min Yao, Hideaki Oikawa y Isao Tanaka. "Structure analysis of geranyl pyrophosphate methyltransferase and the proposed reaction mechanism of SAM-dependentC-methylation". Acta Crystallographica Section D Biological Crystallography 68, n.º 11 (18 de octubre de 2012): 1558–69. http://dx.doi.org/10.1107/s0907444912038486.
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In the typical isoprenoid-biosynthesis pathway, condensation of the universal C5-unit precursors isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP) occursviathe common intermediates prenyl pyrophosphates (C10–C20). The diversity of isoprenoids reflects differences in chain length, cyclization and further additional modification after cyclization. In contrast, the biosynthesis of 2-methylisonorneol (2-MIB), which is responsible for taste and odour problems in drinking water, is unique in that it primes the enzymatic methylation of geranyl pyrophosphate (GPP) before cyclization, which is catalyzed by anS-adenosyl-L-methionine-dependent methyltransferase (GPPMT). The substrate of GPPMT contains a nonconjugated olefin and the reaction mechanism is expected to be similar to that of the steroid methyltransferase (SMT) family. Here, structural analysis of GPPMT in complex with its cofactor and substrate revealed the mechanisms of substrate recognition and possible enzymatic reaction. Using the structures of these complexes, methyl-group transfer and the subsequent proton-abstraction mechanism are discussed. GPPMT and SMTs contain a conserved glutamate residue that is likely to play a role as a general base. Comparison with the reaction mechanism of the mycolic acid cyclopropane synthase (MACS) family also supports this result. This enzyme represented here is the first model of the enzymaticC-methylation of a nonconjugated olefin in the isoprenoid-biosynthesis pathway. In addition, an elaborate system to avoid methylation of incorrect substrates is proposed.
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Bröker, Jan Niklas, Boje Müller, Dirk Prüfer y Christian Schulze Gronover. "Combinatorial Metabolic Engineering in Saccharomyces cerevisiae for the Enhanced Production of the FPP-Derived Sesquiterpene Germacrene". Bioengineering 7, n.º 4 (24 de octubre de 2020): 135. http://dx.doi.org/10.3390/bioengineering7040135.
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Farnesyl diphosphate (FPP)-derived isoprenoids represent a diverse group of plant secondary metabolites with great economic potential. To enable their efficient production in the heterologous host Saccharomyces cerevisiae, we refined a metabolic engineering strategy using the CRISPR/Cas9 system with the aim of increasing the availability of FPP for downstream reactions. The strategy included the overexpression of mevalonate pathway (MVA) genes, the redirection of metabolic flux towards desired product formation and the knockout of genes responsible for competitive reactions. Following the optimisation of culture conditions, the availability of the improved FPP biosynthesis for downstream reactions was demonstrated by the expression of a germacrene synthase from dandelion. Subsequently, biosynthesis of significant amounts of germacrene-A was observed in the most productive strain compared to the wild type. Thus, the presented strategy is an excellent tool to increase FPP-derived isoprenoid biosynthesis in yeast.
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Moura, Ivan Cruz, Gerhard Wunderlich, Maria L. Uhrig, Alicia S. Couto, Valnice J. Peres, Alejandro M. Katzin y Emı́lia A. Kimura. "Limonene Arrests Parasite Development and Inhibits Isoprenylation of Proteins in Plasmodium falciparum". Antimicrobial Agents and Chemotherapy 45, n.º 9 (1 de septiembre de 2001): 2553–58. http://dx.doi.org/10.1128/aac.45.9.2553-2558.2001.
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ABSTRACT Isoprenylation is an essential protein modification in eukaryotic cells. Herein, we report that in Plasmodium falciparum, a number of proteins were labeled upon incubation of intraerythrocytic forms with either [3H]farnesyl pyrophosphate or [3H]geranylgeranyl pyrophosphate. By thin-layer chromatography, we showed that attached isoprenoids are partially modified to dolichol and other, uncharacterized, residues, confirming active isoprenoid metabolism in this parasite. Incubation of blood-stage P. falciparum treated with the isoprenylation inhibitor limonene significantly decreased the parasites' progression from the ring stage to the trophozoite stage and at 1.22 mM, 50% of the parasites died after the first cycle. Using Ras- and Rap-specific monoclonal antibodies, putative Rap and Ras proteins of P. falciparum were immunoprecipitated. Upon treatment with 0.5 mM limonene, isoprenylation of these proteins was significantly decreased, possibly explaining the observed arrest of parasite development.
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Primak, Yuliya A., Mai Du, Michael C. Miller, Derek H. Wells, Alex T. Nielsen, Walter Weyler y Zachary Q. Beck. "Characterization of a Feedback-Resistant Mevalonate Kinase from the Archaeon Methanosarcina mazei". Applied and Environmental Microbiology 77, n.º 21 (9 de septiembre de 2011): 7772–78. http://dx.doi.org/10.1128/aem.05761-11.
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ABSTRACTThe mevalonate pathway is utilized for the biosynthesis of isoprenoids in many bacterial, eukaryotic, and archaeal organisms. Based on previous reports of its feedback inhibition, mevalonate kinase (MVK) may play an important regulatory role in the biosynthesis of mevalonate pathway-derived compounds. Here we report the purification, kinetic characterization, and inhibition analysis of the MVK from the archaeonMethanosarcina mazei. The inhibition of theM. mazeiMVK by the following metabolites derived from the mevalonate pathway was explored: dimethylallyl diphosphate (DMAPP), geranyl pyrophosphate (GPP), farnesyl pyrophosphate (FPP), isopentenyl monophosphate (IP), and diphosphomevalonate.M. mazeiMVK was not inhibited by DMAPP, GPP, FPP, diphosphomevalonate, or IP, a proposed intermediate in an alternative isoprenoid pathway present in archaea. Our findings suggest that theM. mazeiMVK represents a distinct class of mevalonate kinases that can be differentiated from previously characterized MVKs based on its inhibition profile.
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Niinemets, Ü., R. K. Monson, A. Arneth, P. Ciccioli, J. Kesselmeier, U. Kuhn, S. M. Noe, J. Peñuelas y M. Staudt. "The emission factor of volatile isoprenoids: caveats, model algorithms, response shapes and scaling". Biogeosciences Discussions 7, n.º 1 (17 de febrero de 2010): 1233–93. http://dx.doi.org/10.5194/bgd-7-1233-2010.
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Abstract. In models of plant volatile isoprenoid emissions, the instantaneous compound emission rate typically scales with the plant's emission capacity under specified environmental conditions, also defined as the emission factor, ES. In the most widely employed plant isoprenoid emission models, the algorithms developed by Guenther and colleagues (1991, 1993), instantaneous variation of the steady-state emission rate is described as the product of ES and light and temperature response functions. When these models are employed in the in atmospheric chemistry modeling community, species-specific ES values and parameter values defining the instantaneous response curves are typically considered as constant. In the current review, we argue that ES is largely a modeling concept, importantly depending on our understanding of which environmental factors affect isoprenoid emissions, and consequently need standardization during ES determination. In particular, there is now increasing consensus that variations in atmospheric CO2 concentration, in addition to variations in light and temperature, need to be included in the emission models. Furthermore, we demonstrate that for less volatile isoprenoids, mono- and sesquiterpenes, the emissions are often jointly controlled by the compound synthesis and volatility, and because of these combined biochemical and physico-chemical properties, specification of ES as a constant value is incapable of describing instantaneous emissions within the sole assumptions of fluctuating light and temperature, as are used in the standard algorithms. The definition of ES also varies depending on the degree of aggregation of ES values in different parameterization schemes (leaf- vs. canopy- or region-level, species vs. plant functional type level), and various aggregated ES schemes are not compatible for different integration models. The summarized information collectively emphasizes the need to update model algorithms by including missing environmental and physico-chemical controls, and always to define ES within the proper context of model structure and spatial and temporal resolution.
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Niinemets, Ü., R. K. Monson, A. Arneth, P. Ciccioli, J. Kesselmeier, U. Kuhn, S. M. Noe, J. Peñuelas y M. Staudt. "The leaf-level emission factor of volatile isoprenoids: caveats, model algorithms, response shapes and scaling". Biogeosciences 7, n.º 6 (1 de junio de 2010): 1809–32. http://dx.doi.org/10.5194/bg-7-1809-2010.
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Abstract. In models of plant volatile isoprenoid emissions, the instantaneous compound emission rate typically scales with the plant's emission potential under specified environmental conditions, also called as the emission factor, ES. In the most widely employed plant isoprenoid emission models, the algorithms developed by Guenther and colleagues (1991, 1993), instantaneous variation of the steady-state emission rate is described as the product of ES and light and temperature response functions. When these models are employed in the atmospheric chemistry modeling community, species-specific ES values and parameter values defining the instantaneous response curves are often taken as initially defined. In the current review, we argue that ES as a characteristic used in the models importantly depends on our understanding of which environmental factors affect isoprenoid emissions, and consequently need standardization during experimental ES determinations. In particular, there is now increasing consensus that in addition to variations in light and temperature, alterations in atmospheric and/or within-leaf CO2 concentrations may need to be included in the emission models. Furthermore, we demonstrate that for less volatile isoprenoids, mono- and sesquiterpenes, the emissions are often jointly controlled by the compound synthesis and volatility. Because of these combined biochemical and physico-chemical drivers, specification of ES as a constant value is incapable of describing instantaneous emissions within the sole assumptions of fluctuating light and temperature as used in the standard algorithms. The definition of ES also varies depending on the degree of aggregation of ES values in different parameterization schemes (leaf- vs. canopy- or region-scale, species vs. plant functional type levels) and various aggregated ES schemes are not compatible for different integration models. The summarized information collectively emphasizes the need to update model algorithms by including missing environmental and physico-chemical controls, and always to define ES within the proper context of model structure and spatial and temporal resolution.
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Wanke, M., K. Skorupinska-Tudek y E. Swiezewska. "Isoprenoid biosynthesis via 1-deoxy-D-xylulose 5-phosphate/2-C-methyl-D-erythritol 4-phosphate (DOXP/MEP) pathway." Acta Biochimica Polonica 48, n.º 3 (30 de septiembre de 2001): 663–72. http://dx.doi.org/10.18388/abp.2001_3901.
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Higher plants, several algae, bacteria, some strains of Streptomyces and possibly malaria parasite Plasmodium falciparum contain the novel, plastidic DOXP/MEP pathway for isoprenoid biosynthesis. This pathway, alternative with respect to the classical mevalonate pathway, starts with condensation of pyruvate and glyceraldehyde-3-phosphate which yields 1-deoxy-D-xylulose 5-phosphate (DOXP); the latter product can be converted to isopentenyl diphosphate (IPP) and eventually to isoprenoids or thiamine and pyridoxal. Subsequent reactions of this pathway involve transformation of DOXP to 2-C-methyl-D-erythritol 4-phosphate (MEP) which after condensation with CTP forms 4-diphosphocytidyl-2-amethyl-D-erythritol (CDP-ME). Then CDP-ME is phosphorylated to 4-diphosphocytidyl-2-amethyl-D-erythritol 2-phosphate (CDP-ME2P) and to 2-C-methyl-D-erythritol-2,4-cyclodiphosphate (ME-2,4cPP) which is the last known intermediate of the DOXP/MEP pathway. For- mation of IPP and dimethylallyl diphosphate (DMAPP) from ME-2,4cPP still requires clarification. This novel pathway appears to be involved in biosynthesis of carotenoids, phytol (side chain of chlorophylls), isoprene, mono-, di-, tetraterpenes and plastoquinone whereas the mevalonate pathway is responsible for formation of sterols, sesquiterpenes and triterpenes. Several isoprenoids were found to be of mixed origin suggesting that some exchange and/or cooperation exists between these two pathways of different biosynthetic origin. Contradictory results described below could indicate that these two pathways are operating under different physiological conditions of the cell and are dependent on the developmental state of plastids.
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Wei, Lisha, Yan-Yan Zheng, Jie Sun, Pei Wang, Tao Tao, Yeqiong Li, Xin Chen et al. "GGPP depletion initiates metaflammation through disequilibrating CYB5R3-dependent eicosanoid metabolism". Journal of Biological Chemistry 295, n.º 47 (10 de septiembre de 2020): 15988–6001. http://dx.doi.org/10.1074/jbc.ra120.015020.
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Metaflammation is a primary inflammatory complication of metabolic disorders characterized by altered production of many inflammatory cytokines, adipokines, and lipid mediators. Whereas multiple inflammation networks have been identified, the mechanisms by which metaflammation is initiated have long been controversial. As the mevalonate pathway (MVA) produces abundant bioactive isoprenoids and abnormal MVA has a phenotypic association with inflammation/immunity, we speculate that isoprenoids from the MVA may provide a causal link between metaflammation and metabolic disorders. Using a line with the MVA isoprenoid producer geranylgeranyl diphosphate synthase (GGPPS) deleted, we find that geranylgeranyl pyrophosphate (GGPP) depletion causes an apparent metaflammation as evidenced by abnormal accumulation of fatty acids, eicosanoid intermediates, and proinflammatory cytokines. We also find that GGPP prenylate cytochrome b5 reductase 3 (CYB5R3) and the prenylated CYB5R3 then translocate from the mitochondrial to the endoplasmic reticulum (ER) pool. As CYB5R3 is a critical NADH-dependent reductase necessary for eicosanoid metabolism in ER, we thus suggest that GGPP-mediated CYB5R3 prenylation is necessary for metabolism. In addition, we observe that pharmacological inhibition of the MVA pathway by simvastatin is sufficient to inhibit CYB5R3 translocation and induces smooth muscle death. Therefore, we conclude that the dysregulation of MVA intermediates is an essential mechanism for metaflammation initiation, in which the imbalanced production of eicosanoid intermediates in the ER serve as an important pathogenic factor. Moreover, the interplay of MVA and eicosanoid metabolism as we reported here illustrates a model for the coordinating regulation among metabolite pathways.