Journal articles: 'Polyketides'

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Witzig, Reto M., and Christof Sparr. "Synthesis of Enantioenriched Tetra-ortho-3,3′-substituted Biaryls by Small-Molecule-Catalyzed Noncanonical Polyketide Cyclizations." Synlett 31, no. 01 (October 22, 2019): 13–20. http://dx.doi.org/10.1055/s-0039-1690215.

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The arene-forming aldol condensation is a fundamental reaction in the biosynthesis of aromatic polyketides. Precisely controlled by the polyketide synthases, the highly reactive poly-β-carbonyl substrates are diverged into numerous aromatic natural products by selective cyclization reactions; a fascinating biosynthetic strategy that sparked our interest to investigate atroposelective aldol condensations. In this Account, we contextualize and highlight the ability of small-molecule catalysts to selectively convert noncanonical hexacarbonyl substrates in a double arene-forming aldol condensation resulting in the atroposelective synthesis of tetra-ortho-3,3′-substituted biaryls. The hexacarbonyl substrates were obtained by a fourfold ozonolysis enabling a late-stage introduction of all carbonyl functions in one step. Secondary amine catalysts capable of forming an extended hydrogen-bonding network triggered the noncanonical polyketide cyclization in order to form valuable biaryls in high yields and with stereocontrol of up to 98:2 er.1 Biosynthesis of Aromatic Polyketides2 Rotationally Restricted Aromatic Polyketides3 3,3′-Substituted Binaphthalenes in Catalysis4 Stereoselective Synthesis of Atropisomers5 Synthesis of Enantioenriched Tetra-ortho-3,3′-Substituted Biaryls by the Atroposelective Arene-Forming Aldol Condensation6 Conclusion

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Wang, Li, Hui Lu, and Yuanying Jiang. "Natural Polyketides Act as Promising Antifungal Agents." Biomolecules 13, no. 11 (October 24, 2023): 1572. http://dx.doi.org/10.3390/biom13111572.

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Invasive fungal infections present a significant risk to human health. The current arsenal of antifungal drugs is hindered by drug resistance, limited antifungal range, inadequate safety profiles, and low oral bioavailability. Consequently, there is an urgent imperative to develop novel antifungal medications for clinical application. This comprehensive review provides a summary of the antifungal properties and mechanisms exhibited by natural polyketides, encompassing macrolide polyethers, polyether polyketides, xanthone polyketides, linear polyketides, hybrid polyketide non-ribosomal peptides, and pyridine derivatives. Investigating natural polyketide compounds and their derivatives has demonstrated their remarkable efficacy and promising clinical application as antifungal agents.

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Risdian, Chandra, Tjandrawati Mozef, and Joachim Wink. "Biosynthesis of Polyketides in Streptomyces." Microorganisms 7, no. 5 (May 6, 2019): 124. http://dx.doi.org/10.3390/microorganisms7050124.

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Polyketides are a large group of secondary metabolites that have notable variety in their structure and function. Polyketides exhibit a wide range of bioactivities such as antibacterial, antifungal, anticancer, antiviral, immune-suppressing, anti-cholesterol, and anti-inflammatory activity. Naturally, they are found in bacteria, fungi, plants, protists, insects, mollusks, and sponges. Streptomyces is a genus of Gram-positive bacteria that has a filamentous form like fungi. This genus is best known as one of the polyketides producers. Some examples of polyketides produced by Streptomyces are rapamycin, oleandomycin, actinorhodin, daunorubicin, and caprazamycin. Biosynthesis of polyketides involves a group of enzyme activities called polyketide synthases (PKSs). There are three types of PKSs (type I, type II, and type III) in Streptomyces responsible for producing polyketides. This paper focuses on the biosynthesis of polyketides in Streptomyces with three structurally-different types of PKSs.

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Yang, Dongsoo, Hyunmin Eun, and Cindy Pricilia Surya Prabowo. "Metabolic Engineering and Synthetic Biology Approaches for the Heterologous Production of Aromatic Polyketides." International Journal of Molecular Sciences 24, no. 10 (May 18, 2023): 8923. http://dx.doi.org/10.3390/ijms24108923.

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Polyketides are a diverse set of natural products with versatile applications as pharmaceuticals, nutraceuticals, and cosmetics, to name a few. Of several types of polyketides, aromatic polyketides comprising type II and III polyketides contain many chemicals important for human health such as antibiotics and anticancer agents. Most aromatic polyketides are produced from soil bacteria or plants, which are difficult to engineer and grow slowly in industrial settings. To this end, metabolic engineering and synthetic biology have been employed to efficiently engineer heterologous model microorganisms for enhanced production of important aromatic polyketides. In this review, we discuss the recent advancement in metabolic engineering and synthetic biology strategies for the production of type II and type III polyketides in model microorganisms. Future challenges and prospects of aromatic polyketide biosynthesis by synthetic biology and enzyme engineering approaches are also discussed.

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Klopries, Stephan, Uschi Sundermann, and Frank Schulz. "Quantification ofN-acetylcysteamine activated methylmalonate incorporation into polyketide biosynthesis." Beilstein Journal of Organic Chemistry 9 (April 5, 2013): 664–74. http://dx.doi.org/10.3762/bjoc.9.75.

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Polyketides are biosynthesized through consecutive decarboxylative Claisen condensations between a carboxylic acid and differently substituted malonic acid thioesters, both tethered to the giant polyketide synthase enzymes. Individual malonic acid derivatives are typically required to be activated as coenzyme A-thioesters prior to their enzyme-catalyzed transfer onto the polyketide synthase. Control over the selection of malonic acid building blocks promises great potential for the experimental alteration of polyketide structure and bioactivity. One requirement for this endeavor is the supplementation of the bacterial polyketide fermentation system with tailored synthetic thioester-activated malonates. The membrane permeableN-acetylcysteamine has been proposed as a coenzyme A-mimic for this purpose. Here, the incorporation efficiency into different polyketides ofN-acetylcysteamine activated methylmalonate is studied and quantified, showing a surprisingly high and transferable activity of these polyketide synthase substrate analogues in vivo.

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Rodríguez-Berríos, Raúl R., Agnes M. Ríos-Delgado, Amanda P. Perdomo-Lizardo, Andrés E. Cardona-Rivera, Ángel G. Vidal-Rosado, Guillermo A. Narváez-Lozano, Iván A. Nieves-Quiñones, et al. "Extraction, Isolation, Characterization, and Bioactivity of Polypropionates and Related Polyketide Metabolites from the Caribbean Region." Antibiotics 12, no. 7 (June 22, 2023): 1087. http://dx.doi.org/10.3390/antibiotics12071087.

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The Caribbean region is a hotspot of biodiversity (i.e., algae, sponges, corals, mollusks, microorganisms, cyanobacteria, and dinoflagellates) that produces secondary metabolites such as polyketides and polypropionates. Polyketides are a diverse class of natural products synthesized by organisms through a biosynthetic pathway catalyzed by polyketide synthase (PKS). This group of compounds is subdivided into fatty acids, aromatics, and polypropionates such as macrolides, and linear and cyclic polyethers. Researchers have studied the Caribbean region to find natural products and focused on isolation, purification, structural characterization, synthesis, and conducting biological assays against parasites, cancer, fungi, and bacteria. These studies have been summarized in this review, including research from 1981 to 2020. This review includes about 90 compounds isolated in the Caribbean that meet the structural properties of polyketides. Out of 90 compounds presented, 73 have the absolute stereochemical configuration, and 82 have shown biological activity. We expect to motivate the researchers to continue exploring the Caribbean region’s marine environments to discover and investigate new polyketide and polypropionate natural products.

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Sayari, Mohammad, Aria Dolatabadian, Mohamed El-Shetehy, Pawanpuneet Kaur Rehal, and Fouad Daayf. "Genome-Based Analysis of Verticillium Polyketide Synthase Gene Clusters." Biology 11, no. 9 (August 23, 2022): 1252. http://dx.doi.org/10.3390/biology11091252.

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Polyketides are structurally diverse and physiologically active secondary metabolites produced by many organisms, including fungi. The biosynthesis of polyketides from acyl-CoA thioesters is catalyzed by polyketide synthases, PKSs. Polyketides play roles including in cell protection against oxidative stress, non-constitutive (toxic) roles in cell membranes, and promoting the survival of the host organisms. The genus Verticillium comprises many species that affect a wide range of organisms including plants, insects, and other fungi. Many are known as causal agents of Verticillium wilt diseases in plants. In this study, a comparative genomics approach involving several Verticillium species led us to evaluate the potential of Verticillium species for producing polyketides and to identify putative polyketide biosynthesis gene clusters. The next step was to characterize them and predict the types of polyketide compounds they might produce. We used publicly available sequences from ten species of Verticillium including V. dahliae, V. longisporum, V. nonalfalfae, V. alfalfae, V. nubilum, V. zaregamsianum, V. klebahnii, V. tricorpus, V. isaacii, and V. albo-atrum to identify and characterize PKS gene clusters by utilizing a range of bioinformatic and phylogenetic approaches. We found 32 putative PKS genes and possible clusters in the genomes of Verticillium species. All the clusters appear to be complete and functional. In addition, at least five clusters including putative DHN-melanin-, cytochalasin-, fusarielien-, fujikurin-, and lijiquinone-like compounds may belong to the active PKS repertoire of Verticillium. These results will pave the way for further functional studies to understand the role of these clusters.

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Komaki, Hisayuki, and Tomohiko Tamura. "Profile of PKS and NRPS Gene Clusters in the Genome of Streptomyces cellostaticus NBRC 12849T." Fermentation 9, no. 11 (October 24, 2023): 924. http://dx.doi.org/10.3390/fermentation9110924.

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Polyketides and nonribosomal peptides are major secondary metabolites in members of the genus Streptomyces. Streptomyces cellostaticus is a validly recognized species and the type strain produces cellostatin. However, little is known about whether it has the potential to produce diverse polyketides and nonribosomal peptides. Here, we sequenced the whole genome of S. cellostaticus NBRC 12849T and surveyed polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) gene clusters in the genome. The genome encoded 12 PKS, one NRPS and eight hybrid PKS/NRPS gene clusters. Among the 21 gene clusters, products of 10 gene clusters were annotated to be an annimycin congener, fuelimycins, lankamycin, streptovaricin, spore pigment, flaviolin, foxicin, blasticidin, lankacidin and an incarnatapeptine congener via our bioinformatic analysis. Although the other clusters were orphan and their products were unknown, five of them were predicted to be compounds derived from two independent diketides, a tridecaketide, a triketide and a tetraketide with a cysteine residue, respectively. These results suggest that S. cellostaticus is a source of diverse polyketides and hybrid polyketide/nonribosomal peptides, including unknown and new secondary metabolites.

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Pfeifer, Blaine A., and Chaitan Khosla. "Biosynthesis of Polyketides in Heterologous Hosts." Microbiology and Molecular Biology Reviews 65, no. 1 (March 1, 2001): 106–18. http://dx.doi.org/10.1128/mmbr.65.1.106-118.2001.

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SUMMARY Polyketide natural products show great promise as medicinal agents. Typically the products of microbial secondary biosynthesis, polyketides are synthesized by an evolutionarily related but architecturally diverse family of multifunctional enzymes called polyketide synthases. A principal limitation for fundamental biochemical studies of these modular megasynthases, as well as for their applications in biotechnology, is the challenge associated with manipulating the natural microorganism that produces a polyketide of interest. To ameliorate this limitation, over the past decade several genetically amenable microbes have been developed as heterologous hosts for polyketide biosynthesis. Here we review the state of the art as well as the difficulties associated with heterologous polyketide production. In particular, we focus on two model hosts, Streptomyces coelicolor and Escherichia coli. Future directions for this relatively new but growing technological opportunity are also discussed.

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Zhang, Wenjun, and Joyce Liu. "Recent Advances in Understanding and Engineering Polyketide Synthesis." F1000Research 5 (February 23, 2016): 208. http://dx.doi.org/10.12688/f1000research.7326.1.

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Polyketides are a diverse group of natural products that form the basis of many important drugs. The engineering of the polyketide synthase (PKS) enzymes responsible for the formation of these compounds has long been considered to have great potential for producing new bioactive molecules. Recent advances in this field have contributed to the understanding of this powerful and complex enzymatic machinery, particularly with regard to domain activity and engineering, unique building block formation and incorporation, and programming rules and limitations. New developments in tools for in vitro biochemical analysis, full-length megasynthase structural studies, and in vivo heterologous expression will continue to improve our fundamental understanding of polyketide synthesis as well as our ability to engineer the production of polyketides.

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Nah, Ji-Hye, Hye-Jin Kim, Han-Na Lee, Mi-Jin Lee, Si-Sun Choi, and Eung-Soo Kim. "Identification and Biotechnological Application of Novel Regulatory Genes Involved inStreptomycesPolyketide Overproduction through Reverse Engineering Strategy." BioMed Research International 2013 (2013): 1–10. http://dx.doi.org/10.1155/2013/549737.

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Polyketide belongs to a family of abundant natural products typically produced by the filamentous soil bacteriaStreptomyces. Similar to the biosynthesis of most secondary metabolites produced in theStreptomycesspecies, polyketide compounds are synthesized through tight regulatory networks in the cell, and thus extremely low levels of polyketides are typically observed in wild-type strains. Although manyStreptomycespolyketides and their derivatives have potential to be used as clinically important pharmaceutical drugs, traditional strain improvement strategies such as random recursive mutagenesis have long been practiced with little understanding of the molecular basis underlying enhanced polyketide production. Recently, identifying, understanding, and applying a novel polyketide regulatory system identified from various Omics approaches, has become an important tool for rationalStreptomycesstrain improvement. In this paper, DNA microarray-driven reverse engineering efforts for improving titers of polyketides are briefly summarized, primarily focusing on our recent results of identification and application of novel global regulatory genes such aswblA, SCO1712, and SCO5426 inStreptomycesspecies. Sequential targeted gene manipulation involved in polyketide biosynthetic reguation synergistically provided an efficient and rational strategy forStreptomycesstrain improvement. Moreover, the engineered regulation-optimizedStreptomycesmutant strain was further used as a surrogate host for heterologous expression of polyketide pathway.

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Zhang, Zhuan, Hai-Xue Pan, and Gong-Li Tang. "New insights into bacterial type II polyketide biosynthesis." F1000Research 6 (February 21, 2017): 172. http://dx.doi.org/10.12688/f1000research.10466.1.

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Bacterial aromatic polyketides, exemplified by anthracyclines, angucyclines, tetracyclines, and pentangular polyphenols, are a large family of natural products with diverse structures and biological activities and are usually biosynthesized by type II polyketide synthases (PKSs). Since the starting point of biosynthesis and combinatorial biosynthesis in 1984–1985, there has been a continuous effort to investigate the biosynthetic logic of aromatic polyketides owing to the urgent need of developing promising therapeutic candidates from these compounds. Recently, significant advances in the structural and mechanistic identification of enzymes involved in aromatic polyketide biosynthesis have been made on the basis of novel genetic, biochemical, and chemical technologies. This review highlights the progress in bacterial type II PKSs in the past three years (2013–2016). Moreover, novel compounds discovered or created by genome mining and biosynthetic engineering are also included.

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Chen, Yi-Hua, Chen-Chen Wang, Lisa Greenwell, Uwe Rix, Dirk Hoffmeister, Leo C. Vining, Jürgen Rohr, and Ke-Qian Yang. "Functional Analyses of Oxygenases in Jadomycin Biosynthesis and Identification of JadH as a Bifunctional Oxygenase/Dehydrase." Journal of Biological Chemistry 280, no. 23 (April 6, 2005): 22508–14. http://dx.doi.org/10.1074/jbc.m414229200.

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A novel angucycline metabolite, 2,3-dehydro-UWM6, was identified in a jadH mutant of Streptomyces venezuelae ISP5230. Both UWM6 and 2,3-dehydro-UWM6 could be converted to jadomycin A or B by a ketosynthase α (jadA) mutant of S. venezuelae. These angucycline intermediates were also converted to jadomycin A by transformant of the heterologous host Streptomyces lividans expressing the jadFGH oxygenases in vivo and by its cell-free extracts in vitro; thus the three gene products JadFGH are implicated in catalysis of the post-polyketide synthase biosynthetic reactions converting UWM6 to jadomycin aglycone. Genetic and biochemical analyses indicate that JadH possesses dehydrase activity, not previously associated with polyketide-modifying oxygenase. Since the formation of aromatic polyketides often requires multiple dehydration steps, bifunctionality of oxygenases modifying aromatic polyketides may be a general phenomenon.

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Markham, Kelly A., Claire M. Palmer, Malgorzata Chwatko, James M. Wagner, Clare Murray, Sofia Vazquez, Arvind Swaminathan, Ishani Chakravarty, Nathaniel A. Lynd, and Hal S. Alper. "Rewiring Yarrowia lipolytica toward triacetic acid lactone for materials generation." Proceedings of the National Academy of Sciences 115, no. 9 (February 12, 2018): 2096–101. http://dx.doi.org/10.1073/pnas.1721203115.

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Polyketides represent an extremely diverse class of secondary metabolites often explored for their bioactive traits. These molecules are also attractive building blocks for chemical catalysis and polymerization. However, the use of polyketides in larger scale chemistry applications is stymied by limited titers and yields from both microbial and chemical production. Here, we demonstrate that an oleaginous organism (specifically, Yarrowia lipolytica) can overcome such production limitations owing to a natural propensity for high flux through acetyl–CoA. By exploring three distinct metabolic engineering strategies for acetyl–CoA precursor formation, we demonstrate that a previously uncharacterized pyruvate bypass pathway supports increased production of the polyketide triacetic acid lactone (TAL). Ultimately, we establish a strain capable of producing over 35% of the theoretical conversion yield to TAL in an unoptimized tube culture. This strain also obtained an averaged maximum titer of 35.9 ± 3.9 g/L with an achieved maximum specific productivity of 0.21 ± 0.03 g/L/h in bioreactor fermentation. Additionally, we illustrate that a β-oxidation-related overexpression (PEX10) can support high TAL production and is capable of achieving over 43% of the theoretical conversion yield under nitrogen starvation in a test tube. Next, through use of this bioproduct, we demonstrate the utility of polyketides like TAL to modify commodity materials such as poly(epichlorohydrin), resulting in an increased molecular weight and shift in glass transition temperature. Collectively, these findings establish an engineering strategy enabling unprecedented production from a type III polyketide synthase as well as establish a route through O-functionalization for converting polyketides into new materials.

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Helfrich, Eric J. N., and Jörn Piel. "Biosynthesis of polyketides by trans-AT polyketide synthases." Natural Product Reports 33, no. 2 (2016): 231–316. http://dx.doi.org/10.1039/c5np00125k.

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This review discusses the biosynthesis of natural products that are generated bytrans-AT polyketide synthases, a family of catalytically versatile enzymes that represents one of the major group of proteins involved in the production of bioactive polyketides.

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Caldara-Festin, Grace, David R. Jackson, Jesus F. Barajas, Timothy R. Valentic, Avinash B. Patel, Stephanie Aguilar, MyChi Nguyen, et al. "Structural and functional analysis of two di-domain aromatase/cyclases from type II polyketide synthases." Proceedings of the National Academy of Sciences 112, no. 50 (December 2, 2015): E6844—E6851. http://dx.doi.org/10.1073/pnas.1512976112.

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Aromatic polyketides make up a large class of natural products with diverse bioactivity. During biosynthesis, linear poly-β-ketone intermediates are regiospecifically cyclized, yielding molecules with defined cyclization patterns that are crucial for polyketide bioactivity. The aromatase/cyclases (ARO/CYCs) are responsible for regiospecific cyclization of bacterial polyketides. The two most common cyclization patterns are C7–C12 and C9–C14 cyclizations. We have previously characterized three monodomain ARO/CYCs: ZhuI, TcmN, and WhiE. The last remaining uncharacterized class of ARO/CYCs is the di-domain ARO/CYCs, which catalyze C7–C12 cyclization and/or aromatization. Di-domain ARO/CYCs can further be separated into two subclasses: “nonreducing” ARO/CYCs, which act on nonreduced poly-β-ketones, and “reducing” ARO/CYCs, which act on cyclized C9 reduced poly-β-ketones. For years, the functional role of each domain in cyclization and aromatization for di-domain ARO/CYCs has remained a mystery. Here we present what is to our knowledge the first structural and functional analysis, along with an in-depth comparison, of the nonreducing (StfQ) and reducing (BexL) di-domain ARO/CYCs. This work completes the structural and functional characterization of mono- and di-domain ARO/CYCs in bacterial type II polyketide synthases and lays the groundwork for engineered biosynthesis of new bioactive polyketides.

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Štiblariková, Mária, Angelika Lásiková, and Tibor Gracza. "Benzyl Alcohol/Salicylaldehyde-Type Polyketide Metabolites of Fungi: Sources, Biosynthesis, Biological Activities, and Synthesis." Marine Drugs 21, no. 1 (December 27, 2022): 19. http://dx.doi.org/10.3390/md21010019.

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Marine microorganisms are an important source of natural polyketides, which have become a significant reservoir of lead structures for drug design due to their diverse biological activities. In this review, we provide a summary of the resources, structures, biological activities, and proposed biosynthetic pathways of the benzyl alcohol/salicylaldehyde-type polyketides. In addition, the total syntheses of these secondary metabolites from their discoveries to the present day are presented. This review could be helpful for researchers in the total synthesis of complex natural products and the use of polyketide bioactive molecules for pharmacological purposes and applications in medicinal chemistry.

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Bai, Xuelian, Yue Sheng, Zhenxing Tang, Jingyi Pan, Shigui Wang, Bin Tang, Ting Zhou, Lu’e Shi, and Huawei Zhang. "Polyketides as Secondary Metabolites from the Genus Aspergillus." Journal of Fungi 9, no. 2 (February 15, 2023): 261. http://dx.doi.org/10.3390/jof9020261.

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Polyketides are an important class of structurally diverse natural products derived from a precursor molecule consisting of a chain of alternating ketone and methylene groups. These compounds have attracted the worldwide attention of pharmaceutical researchers since they are endowed with a wide array of biological properties. As one of the most common filamentous fungi in nature, Aspergillus spp. is well known as an excellent producer of polyketide compounds with therapeutic potential. By extensive literature search and data analysis, this review comprehensively summarizes Aspergillus-derived polyketides for the first time, regarding their occurrences, chemical structures and bioactivities as well as biosynthetic logics.

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Zhao, Shiji, Fanglue Ni, Tianyin Qiu, Jacob T. Wolff, Shiou-Chuan Tsai, and Ray Luo. "Molecular Basis for Polyketide Ketoreductase–Substrate Interactions." International Journal of Molecular Sciences 21, no. 20 (October 13, 2020): 7562. http://dx.doi.org/10.3390/ijms21207562.

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Polyketides are a large class of structurally and functionally diverse natural products with important bioactivities. Many polyketides are synthesized by reducing type II polyketide synthases (PKSs), containing transiently interacting standalone enzymes. During synthesis, ketoreductase (KR) catalyzes regiospecific carbonyl to hydroxyl reduction, determining the product outcome, yet little is known about what drives specific KR–substrate interactions. In this study, computational approaches were used to explore KR–substrate interactions based on previously solved apo and mimic cocrystal structures. We found five key factors guiding KR–substrate binding. First, two major substrate binding motifs were identified. Second, substrate length is the key determinant of substrate binding position. Third, two key residues in chain length specificity were confirmed. Fourth, phosphorylation of substrates is critical for binding. Finally, packing/hydrophobic effects primarily determine the binding stability. The molecular bases revealed here will help further engineering of type II PKSs and directed biosynthesis of new polyketides.

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Prasad. B, Venkata Nagendra, and Latha D. "Investigating the Synergistic Antibacterial Activity of Epiphytic Bacterial Polyketides and Biopolymer Alginates from Marine Microalgae." Journal of University of Shanghai for Science and Technology 23, no. 10 (October 4, 2021): 115–35. http://dx.doi.org/10.51201/jusst/21/09704.

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The objective was framed to analyse the synergistic antibacterial activity and woundhealing ability of the developed polyketide-alginate polymers. Alginates were extracted from a brown seaweed Padina tetrastromatica and used as a synergistic compound along with bacterial polyketides. Polyketides and alginate polymer combinations were used against test bacteria to determine the synergistic antibacterial activity. A novel wound-healing film was developed using polyketide and alginates with synergistic concentrations and its degradability and wound-healing ability was investigated. The findings in the present research showed most significantly that, Staphylococcus aureus showed complete synergy with the mean MIC value of 0.03 μg/ml and with best FIC value of 0.24 (p<0.5). Degradation of developed films revealed that more moisture leads to more release of antibacterial alginate content at the wound site and hence more degradation. This was evident from the FESEM analysis. In vitro wound-healing assay revealed that the developed polyketide-alginate polymers exhibited cell migration and proliferation after 24th hour of incubation at 370C indicating the wound-healing abilities. Hence, it can be concluded that the biochemical compounds present in the developed polyketide-alginate polymers are considered highly significant in treating any types of wounds.

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Metsä-Ketelä, Mikko, Laura Halo, Eveliina Munukka, Juha Hakala, Pekka Mäntsälä, and Kristiina Ylihonko. "Molecular Evolution of Aromatic Polyketides and Comparative Sequence Analysis of Polyketide Ketosynthase and 16S Ribosomal DNA Genes from Various Streptomyces Species." Applied and Environmental Microbiology 68, no. 9 (September 2002): 4472–79. http://dx.doi.org/10.1128/aem.68.9.4472-4479.2002.

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ABSTRACT A 613-bp fragment of an essential ketosynthase gene from the biosynthetic pathway of aromatic polyketide antibiotics was sequenced from 99 actinomycetes isolated from soil. Phylogenetic analysis showed that the isolates clustered into clades that correspond to the various classes of aromatic polyketides. Additionally, sequencing of a 120-bp fragment from the γ-variable region of 16S ribosomal DNA (rDNA) and subsequent comparative sequence analysis revealed incongruity between the ketosynthase and 16S rDNA phylogenetic trees, which strongly suggests that there has been horizontal transfer of aromatic polyketide biosynthesis genes. The results show that the ketosynthase tree could be used for DNA fingerprinting of secondary metabolites and for screening interesting aromatic polyketide biosynthesis genes. Furthermore, the movement of the ketosynthase genes suggests that traditional marker molecules like 16S rDNA give misleading information about the biosynthesis potential of aromatic polyketides, and thus only molecules that are directly involved in the biosynthesis of secondary metabolites can be used to gain information about the biodiversity of antibiotic production in different actinomycetes.

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Tsai, Shiou-Chuan (Sheryl). "The Structural Enzymology of Iterative Aromatic Polyketide Synthases: A Critical Comparison with Fatty Acid Synthases." Annual Review of Biochemistry 87, no. 1 (June 20, 2018): 503–31. http://dx.doi.org/10.1146/annurev-biochem-063011-164509.

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Polyketides are a large family of structurally complex natural products including compounds with important bioactivities. Polyketides are biosynthesized by polyketide synthases (PKSs), multienzyme complexes derived evolutionarily from fatty acid synthases (FASs). The focus of this review is to critically compare the properties of FASs with iterative aromatic PKSs, including type II PKSs and fungal type I nonreducing PKSs whose chemical logic is distinct from that of modular PKSs. This review focuses on structural and enzymological studies that reveal both similarities and striking differences between FASs and aromatic PKSs. The potential application of FAS and aromatic PKS structures for bioengineering future drugs and biofuels is highlighted.

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Araki, Tsuyoshi, and Tamao Saito. "Small molecules and cell differentiation in Dictyostelium discoideum." International Journal of Developmental Biology 63, no. 8-9-10 (2019): 429–38. http://dx.doi.org/10.1387/ijdb.190192ts.

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Dictyostelium is a microorganism found in soils that are known as the battle fields of chemical warfare. Genome analysis of Dictyostelium revealed that it has great potential for the production of small molecules, including secondary metabolites such as polyketides and terpenes.Polyketides are a large family of secondary metabolites which have a variety of structures. In accordance with their structural variety, polyketides have a plethora of biological activities, including antimicrobial, antifungal, and antitumor activities. Unsurprisingly, they have exceptional medical importance. Polyketides in nature work as protective compounds and /or function in pheromonal communication. Terpenes belong to another family of structurally diverse secondary metabolites which play roles in ecological interactions, including defence against predators and formation of mutually beneficial alliance with other organisms. Polyketides and terpenes work as intra- or inter-species signalling compounds, i.e. they play the role of a chemical language. However, in Dictyostelium, they work as paracrine signalling compounds which control the organism’s multicellular morphogenesis. This review is primarily focused on the small molecules that regulate pattern formation in the slug stage of the organism and their biosynthetic pathways. Current in vivo understandings of polyketide DIF-1 induced cell differentiation and DIF-1-dependent/independent pathways are also discussed.

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Piel, Jörn. "Biosynthesis of polyketides by trans-AT polyketide synthases." Natural Product Reports 27, no. 7 (2010): 996. http://dx.doi.org/10.1039/b816430b.

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Zheng, Jianting, and Adrian T. Keatinge-Clay. "The status of type I polyketide synthase ketoreductases." MedChemComm 4, no. 1 (2013): 34–40. http://dx.doi.org/10.1039/c2md20191g.

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The functional dissection of type I polyketide synthases has established that ketoreductases most commonly set the orientations of the hydroxyl and alkyl substituents of complex polyketides. Here we review the biochemical, structural biology, and engineering studies that have helped elucidate how stereocontrol is enforced by these enzymes.

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Guo, Xiaoxiao, Fusheng Chen, Jiao Liu, Yanchun Shao, Xiaohong Wang, and Youxiang Zhou. "Genome Mining and Analysis of PKS Genes in Eurotium cristatum E1 Isolated from Fuzhuan Brick Tea." Journal of Fungi 8, no. 2 (February 16, 2022): 193. http://dx.doi.org/10.3390/jof8020193.

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Eurotium cristatum as the dominant fungi species of Fuzhuan brick tea in China, can produce multitudinous secondary metabolites (SMs) with various bioactivities. Polyketides are a very important class of SMs found in E. cristatum and have gained extensive attention in recent years due to their remarkable diversity of structures and multiple functions. Therefore, it is necessary to explore the polyketides produced by E. cristatum at the genomic level to enhance its application value. In this paper, 12 polyketide synthase (PKS) genes were found in the whole genome of E. cristatum E1 isolated from Fuzhuan brick tea. In addition, the qRT-PCR results further demonstrated that these genes were expressed. Moreover, metabolic analysis demonstrated E. cristatum E1 can produce a variety of polyketides, including citreorosein, emodin, physcion, isoaspergin, dihydroauroglaucin, iso-dihydroauroglaucin, aspergin, flavoglaucin and auroglaucin. Furthermore, based on genomic analysis, the putative secondary metabolites clusters for emodin and flavoglaucin were proposed. The results reported here will lay a good basis for systematically mining SMs resources of E. cristatum and broadening its application fields.

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Zhang, Wenjun, Brian D. Ames, Shiou-Chuan Tsai, and Yi Tang. "Engineered Biosynthesis of a Novel Amidated Polyketide, Using the Malonamyl-Specific Initiation Module from the Oxytetracycline Polyketide Synthase." Applied and Environmental Microbiology 72, no. 4 (April 2006): 2573–80. http://dx.doi.org/10.1128/aem.72.4.2573-2580.2006.

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ABSTRACT Tetracyclines are aromatic polyketides biosynthesized by bacterial type II polyketide synthases (PKSs). Understanding the biochemistry of tetracycline PKSs is an important step toward the rational and combinatorial manipulation of tetracycline biosynthesis. To this end, we have sequenced the gene cluster of oxytetracycline (oxy and otc genes) PKS genes from Streptomyces rimosus. Sequence analysis revealed a total of 21 genes between the otrA and otrB resistance genes. We hypothesized that an amidotransferase, OxyD, synthesizes the malonamate starter unit that is a universal building block for tetracycline compounds. In vivo reconstitution using strain CH999 revealed that the minimal PKS and OxyD are necessary and sufficient for the biosynthesis of amidated polyketides. A novel alkaloid (WJ35, or compound 2) was synthesized as the major product when the oxy-encoded minimal PKS, the C-9 ketoreductase (OxyJ), and OxyD were coexpressed in CH999. WJ35 is an isoquinolone compound derived from an amidated decaketide backbone and cyclized with novel regioselectivity. The expression of OxyD with a heterologous minimal PKS did not afford similarly amidated polyketides, suggesting that the oxy-encoded minimal PKS possesses novel starter unit specificity.

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Bao, Wuli, Paul J. Sheldon, Evelyn Wendt-Pienkowski, and C. Richard Hutchinson. "The Streptomyces peucetius dpsC Gene Determines the Choice of Starter Unit in Biosynthesis of the Daunorubicin Polyketide." Journal of Bacteriology 181, no. 15 (August 1, 1999): 4690–95. http://dx.doi.org/10.1128/jb.181.15.4690-4695.1999.

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ABSTRACT The starter unit used in the biosynthesis of daunorubicin is propionyl coenzyme A (CoA) rather than acetyl-CoA, which is used in the production of most of the bacterial aromatic polyketides studied to date. In the daunorubicin biosynthesis gene cluster ofStreptomyces peucetius, directly downstream of the genes encoding the β-ketoacyl:acyl carrier protein synthase subunits, are two genes, dpsC and dpsD, encoding proteins that are believed to function as the starter unit-specifying enzymes. Recombinant strains containing plasmids carrying dpsC anddpsD, in addition to other daunorubicin polyketide synthase (PKS) genes, incorporate the correct starter unit into polyketides made by these genes, suggesting that, contrary to earlier reports, the enzymes encoded by dpsC and dpsD play a crucial role in starter unit specification. Additionally, the results of a cell-free synthesis of 21-carbon polyketides from propionyl-CoA and malonyl-CoA that used the protein extracts of recombinant strains carrying other daunorubicin PKS genes to which purified DpsC was added suggest that this enzyme has the primary role in starter unit discrimination for daunorubicin biosynthesis.

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Studt, Lena, Philipp Wiemann, Karin Kleigrewe, Hans-Ulrich Humpf, and Bettina Tudzynski. "Biosynthesis of Fusarubins Accounts for Pigmentation of Fusarium fujikuroi Perithecia." Applied and Environmental Microbiology 78, no. 12 (April 6, 2012): 4468–80. http://dx.doi.org/10.1128/aem.00823-12.

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ABSTRACTFusarium fujikuroiproduces a variety of secondary metabolites, of which polyketides form the most diverse group. Among these are the highly pigmented naphthoquinones, which have been shown to possess different functional properties for the fungus. A group of naphthoquinones, polyketides related to fusarubin, were identified inFusariumspp. more than 60 years ago, but neither the genes responsible for their formation nor their biological function has been discovered to date. In addition, although it is known that the sexual fruiting bodies in which the progeny of the fungus develops are darkly colored by a polyketide synthase (PKS)-derived pigment, the structure of this pigment has never been elucidated. Here we present data that link the fusarubin-type polyketides to a defined gene cluster, which we designatefsr, and demonstrate that the fusarubins are the pigments responsible for the coloration of the perithecia. We studied their regulation and the function of the single genes within the cluster by a combination of gene replacements and overexpression of the PKS-encoding gene, and we present a model for the biosynthetic pathway of the fusarubins based on these data.

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Milke, Lars, and Jan Marienhagen. "Engineering intracellular malonyl-CoA availability in microbial hosts and its impact on polyketide and fatty acid synthesis." Applied Microbiology and Biotechnology 104, no. 14 (May 8, 2020): 6057–65. http://dx.doi.org/10.1007/s00253-020-10643-7.

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AbstractMalonyl-CoA is an important central metabolite serving as the basic building block for the microbial synthesis of many pharmaceutically interesting polyketides, but also fatty acid–derived compounds including biofuels. Especially Saccharomyces cerevisiae, Escherichia coli, and Corynebacterium glutamicum have been engineered towards microbial synthesis of such compounds in recent years. However, developed strains and processes often suffer from insufficient productivity. Usually, tightly regulated intracellular malonyl-CoA availability is regarded as the decisive bottleneck limiting overall product formation. Therefore, metabolic engineering towards improved malonyl-CoA availability is essential to design efficient microbial cell factories for the production of polyketides and fatty acid derivatives. This review article summarizes metabolic engineering strategies to improve intracellular malonyl-CoA formation in industrially relevant microorganisms and its impact on productivity and product range, with a focus on polyketides and other malonyl-CoA-dependent products.Key Points• Malonyl-CoA is the central building block of polyketide synthesis.• Increasing acetyl-CoA supply is pivotal to improve malonyl-CoA availability.• Improved acetyl-CoA carboxylase activity increases availability of malonyl-CoA.• Fatty acid synthesis as an ambivalent target to improve malonyl-CoA supply.

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Komaki, Hisayuki, Ryosuke Fudou, Takashi Iizuka, Daisuke Nakajima, Koei Okazaki, Daisuke Shibata, Makoto Ojika, and Shigeaki Harayama. "PCR Detection of Type I Polyketide Synthase Genes in Myxobacteria." Applied and Environmental Microbiology 74, no. 17 (July 7, 2008): 5571–74. http://dx.doi.org/10.1128/aem.00224-08.

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ABSTRACT The diversity of type I modular polyketide synthase (PKS) was explored by PCR amplification of DNA encoding ketosynthase and acyltransferase domains in myxobacteria. The sequencing of the amplicons revealed that many PKS genes were distantly related to the published sequences. Thus, myxobacteria may be excellent resources for novel and diverse polyketides.

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Yang, Xinmei, Takashi Matsui, Takahiro Mori, Futoshi Taura, Hiroshi Noguchi, Ikuro Abe, and Hiroyuki Morita. "Expression, purification and crystallization of a plant polyketide cyclase fromCannabis sativa." Acta Crystallographica Section F Structural Biology Communications 71, no. 12 (November 18, 2015): 1470–74. http://dx.doi.org/10.1107/s2053230x15020385.

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Plant polyketides are a structurally diverse family of natural products. In the biosynthesis of plant polyketides, the construction of the carbocyclic scaffold is a key step in diversifying the polyketide structure. Olivetolic acid cyclase (OAC) fromCannabis sativaL. is the only known plant polyketide cyclase that catalyzes the C2–C7 intramolecular aldol cyclization of linear pentyl tetra-β-ketide-CoA to generate olivetolic acid in the biosynthesis of cannabinoids. The enzyme is also thought to belong to the dimeric α+β barrel (DABB) protein family. However, because of a lack of functional analysis of other plant DABB proteins and low sequence identity with the functionally distinct bacterial DABB proteins, the catalytic mechanism of OAC has remained unclear. To clarify the intimate catalytic mechanism of OAC, the enzyme was overexpressed inEscherichia coliand crystallized using the vapour-diffusion method. The crystals diffracted X-rays to 1.40 Å resolution and belonged to space groupP3121 orP3221, with unit-cell parametersa=b= 47.3,c= 176.0 Å. Further crystallographic analysis will provide valuable insights into the structure–function relationship and catalytic mechanism of OAC.

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Ray, Lauren, and Bradley S. Moore. "Recent advances in the biosynthesis of unusual polyketide synthase substrates." Natural Product Reports 33, no. 2 (2016): 150–61. http://dx.doi.org/10.1039/c5np00112a.

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Polyketides comprise a diverse class of natural products, with many important biological and pharmacological activities. Substrates functioning as starter units and extender units during their assembly significantly contribute to the chemical complexity exhibited by this class of natural products. This highlight provides an overview of the recent advances in understanding the diversity of these polyketide synthase (PKS) building blocks.

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Yang, Yin-He, Da-Song Yang, Hong-Mei Lei, Cheng-Yun Li, Guo-Hong Li, and Pei-Ji Zhao. "Griseaketides A–D, New Aromatic Polyketides from the Pathogenic Fungus Magnaporthe grisea." Molecules 25, no. 1 (December 24, 2019): 72. http://dx.doi.org/10.3390/molecules25010072.

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Magnaporthe grisea is the causal agent of rice blast disease, which is the most serious disease of cultivated rice. Aromatic polyketides are its typical metabolites and are involved in the infection process. In the search for novel lead compounds, chemical investigation of the fungus M. grisea M639 has led to the isolation of four new aromatic polyketides (salicylaldehyde skeleton bearing an unsaturated side chain), griseaketides A–D (1–4), as well as 15 known compounds (5–19). The structures of the new compounds were elucidated on the basis of extensive spectroscopic analyses, including HR-MS, 2D NMR. Compound 12 showed prominent activity that killed 94.5% of C. elegans at 400 ppm and 66.9% at 200 ppm over 24 h. This is the first report describing the nematicidal activity of this type aromatic polyketide.

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Chen, Chunmei, Xue Ren, Huaming Tao, Wenteng Cai, Yuchi Chen, Xiaowei Luo, Peng Guo, and Yonghong Liu. "Anti-Inflammatory Polyketides from an Alga-Derived Fungus Aspergillus ochraceopetaliformis SCSIO 41020." Marine Drugs 20, no. 5 (April 27, 2022): 295. http://dx.doi.org/10.3390/md20050295.

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A new linear polyketide, named aspormisin A (1), together with five known polyketides (2–6), were isolated from the alga-derived fungus Aspergillus ochraceopetaliformis SCSIO 41020. Their structures were elucidated through a detailed comprehensive spectroscopic analysis, as well as a comparison with the literature. An anti-inflammatory evaluation showed that compounds 2, 5, and 6 possessed inhibitory activity against the excessive production of nitric oxide (NO) and pro-inflammatory cytokines in LPS-treated RAW 264.7 macrophages in a dose-dependent manner without cytotoxicity. Further studies revealed that compound 2 was active in blocking the release of pro-inflammatory cytokines (IL-6, MCP-1, and TNF-α) induced by LPS both in vivo and in vitro. Our findings provide a basis for the further development of linear polyketides as promising anti-inflammatory agents.

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Go, Maybelle Kho, Jantana Wongsantichon, Vivian Wing Ngar Cheung, Jeng Yeong Chow, Robert C. Robinson, and Wen Shan Yew. "Synthetic Polyketide Enzymology: Platform for Biosynthesis of Antimicrobial Polyketides." ACS Catalysis 5, no. 7 (June 4, 2015): 4033–42. http://dx.doi.org/10.1021/acscatal.5b00477.

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Carreras, Christopher W., and Daniel V. Santi. "Engineering of modular polyketide synthases to produce novel polyketides." Current Opinion in Biotechnology 9, no. 4 (August 1998): 403–11. http://dx.doi.org/10.1016/s0958-1669(98)80015-3.

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Kunnari, Tero, Kristiina Ylihonko, Anne Hautala, Karel D. Klika, Pekka Mäntsälä, and Juha Hakala. "Incorrectly folded aromatic polyketides from polyketide reductase deficient mutants." Bioorganic & Medicinal Chemistry Letters 9, no. 18 (September 1999): 2639–42. http://dx.doi.org/10.1016/s0960-894x(99)00439-4.

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Yu, Tin-Wein, Yuemao Shen, Robert McDaniel, Heinz G. Floss, Chaitan Khosla, David A. Hopwood, and Bradley S. Moore. "Engineered Biosynthesis of Novel Polyketides fromStreptomycesSpore Pigment Polyketide Synthases." Journal of the American Chemical Society 120, no. 31 (August 1998): 7749–59. http://dx.doi.org/10.1021/ja9803658.

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Giri, Gorkha Raj, and Priti Saxena. "Mycobacterial MMAR_2193 catalyzes O-methylation of diverse polyketide cores." PLOS ONE 17, no. 1 (January 5, 2022): e0262241. http://dx.doi.org/10.1371/journal.pone.0262241.

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O-methylation of small molecules is a common modification widely present in most organisms. Type III polyketides undergo O-methylation at hydroxyl end to play a wide spectrum of roles in bacteria, plants, algae, and fungi. Mycobacterium marinum harbours a distinctive genomic cluster with a type III pks gene and genes for several polyketide modifiers including a methyltransferase gene, mmar_2193. This study reports functional analyses of MMAR_2193 and reveals multi-methylating potential of the protein. Comparative sequence analyses revealed conservation of catalytically important motifs in MMAR_2193 protein. Homology-based structure-function and molecular docking studies suggested type III polyketide cores as possible substrates for MMAR_2193 catalysis. In vitro enzymatic characterization revealed the capability of MMAR_2193 protein to utilize diverse polyphenolic substrates to methylate several hydroxyl positions on a single substrate molecule. High-resolution mass spectrometric analyses identified multi-methylations of type III polyketides in cell-free reconstitution assays. Notably, our metabolomics analyses identified some of these methylated molecules in biofilms of wild type Mycobacterium marinum. This study characterizes a novel mycobacterial O-methyltransferase protein with multi-methylating enzymatic ability that could be exploited to generate a palette of structurally distinct bioactive molecules.

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Essig, Sebastian, and Dirk Menche. "Stereochemistry and total synthesis of complex myxobacterial macrolides." Pure and Applied Chemistry 85, no. 6 (March 15, 2013): 1103–20. http://dx.doi.org/10.1351/pac-con-12-09-12.

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Polyketides are a very diverse family of natural products with an extremely broad range of biological activities and pharmacological properties, including antiproliferative, antibiotic, antifungal, or antiplasmodial activities, and in many cases specific targets are addressed at the molecular level. Their structures are characterized by diverse assemblies of methyl- and hydroxyl-bearing stereogenic centers enabling large numbers of stereochemical permutations, which are often embedded into macrolide rings. This complexity renders the stereochemical assignment and directed total synthesis challenging tasks. Within this review, we will detail practicable approaches for the stereochemical determination of diverse complex polyketides of myxobacterial origin by using computational and NMR methods in combination with novel procedures based on bioinformatics. Furthermore, we have developed efficient preparative strategies for the synthesis of these compounds, which have culminated in several first total syntheses. Key aspects of these various endeavors, which will also focus on the importance of conformational bias in complex polyketide analysis and synthesis, will be discussed within this review in the realm of the potent macrolide antibiotics etnangien and rhizopodin. Along these lines, we will also summarize novel methods for the rapid assembly of key structural elements of polyketides including a novel domino concept relying on a combination of a nucleophilic addition and a Tsuji–Trost reaction.

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Bennett, J. W. "From molecular genetics and secondary metabolism to molecular metabolites and secondary genetics." Canadian Journal of Botany 73, S1 (December 31, 1995): 917–24. http://dx.doi.org/10.1139/b95-339.

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Secondary metabolites constitute a huge array of low molecular weight natural products that cannot be easily defined. Largely produced by bacteria, fungi, and green plants, they tend to be synthesized after active growth has ceased, in families of similar compounds, often at the same time as species-specific morphological characters become apparent. Although, in many cases, the function that the secondary metabolite performs in the producing organism is unknown, the bioactivity of these compounds has been exploited since prehistoric times as drugs, poisons, food flavoring agents, and so forth. In fungi, the polyketide family is the largest known group of secondary metabolite compounds. Polyketides are synthesized from acetate by a mechanism analogous to fatty acid biosynthesis but involving changes in oxidation level and stereochemistry during the chain-elongation process. The fungal polyketide biosynthetic pathways for aflatoxin and patulin have emerged as model systems. The use of blocked mutants has been an essential part of the research approach for both pathways. Molecular methods of studying fungal secondary metabolites were first used with penicillin and cephalosporin, both of which are amino acid derived. Most of the basic molecular work on polyketides was done with streptomycete-derived compounds; however, enough fungal data are now available to compare fungal and streptomycete polyketide synthases, as well as to map the genes involved in a number of polyketide pathways from both groups. The traditional dogma, derived from classical genetics, that genes for fungal pathways are unlinked, has been overturned. In addition, cloning of structural genes facilitates the formation of hybrid molecules, and we are on the brink of understanding certain regulatory functions. Key words: fungal metabolism, secondary metabolism, polyketide, β-lactam, product discovery.

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Pieper, Rembert, Guanglin Luo, David E. Cane, and C. Khosla. "Cell-free synthesis of polyketides by recombinant erythromycin polyketide synthases." Nature 378, no. 6554 (November 1995): 263–66. http://dx.doi.org/10.1038/378263a0.

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Chen, Hanna, Zhilong Bian, Vinothkannan Ravichandran, Ruijuan Li, Yi Sun, Liujie Huo, Jun Fu, et al. "Biosynthesis of polyketides by trans-AT polyketide synthases in Burkholderiales." Critical Reviews in Microbiology 45, no. 2 (March 4, 2019): 162–81. http://dx.doi.org/10.1080/1040841x.2018.1514365.

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Zhang, Qi, Bo Pang, Wei Ding, and Wen Liu. "Aromatic Polyketides Produced by Bacterial Iterative Type I Polyketide Synthases." ACS Catalysis 3, no. 7 (May 31, 2013): 1439–47. http://dx.doi.org/10.1021/cs400211x.

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Nakano, Chiaki, Hiroki Ozawa, Genki Akanuma, Nobutaka Funa, and Sueharu Horinouchi. "Biosynthesis of Aliphatic Polyketides by Type III Polyketide Synthase and Methyltransferase in Bacillus subtilis." Journal of Bacteriology 191, no. 15 (May 22, 2009): 4916–23. http://dx.doi.org/10.1128/jb.00407-09.

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ABSTRACT Type III polyketide synthases (PKSs) synthesize a variety of aromatic polyketides in plants, fungi, and bacteria. The bacterial genome projects predicted that probable type III PKS genes are distributed in a wide variety of gram-positive and -negative bacteria. The gram-positive model microorganism Bacillus subtilis contained the bcsA-ypbQ operon, which appeared to encode a type III PKS and a methyltransferase, respectively. Here, we report the characterization of bcsA (renamed bpsA, for Bacillus pyrone synthase, on the basis of its function) and ypbQ, which are involved in the biosynthesis of aliphatic polyketides. In vivo analysis demonstrated that BpsA was a type III PKS catalyzing the synthesis of triketide pyrones from long-chain fatty acyl-coenzyme A (CoA) thioesters as starter substrates and malonyl-CoA as an extender substrate, and YpbQ was a methyltransferase acting on the triketide pyrones to yield alkylpyrone methyl ethers. YpbQ thus was named BpsB because of its functional relatedness to BpsA. In vitro analysis with histidine-tagged BpsA revealed that it used broad starter substrates and produced not only triketide pyrones but also tetraketide pyrones and alkylresorcinols. Although the aliphatic polyketides were expected to localize in the membrane and play some role in modulating the rigidity and properties of the membrane, no detectable phenotypic changes were observed for a B. subtilis mutant containing a whole deletion of the bpsA-bpsB operon.

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Wang, Bin, Fang Guo, Chunshuai Huang, and Huimin Zhao. "Unraveling the iterative type I polyketide synthases hidden in Streptomyces." Proceedings of the National Academy of Sciences 117, no. 15 (March 26, 2020): 8449–54. http://dx.doi.org/10.1073/pnas.1917664117.

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Type I polyketide synthases (T1PKSs) are one of the most extensively studied PKSs, which can act either iteratively or via an assembly-line mechanism. Domains in the T1PKSs can readily be predicted by computational tools based on their highly conserved sequences. However, to distinguish between iterative and noniterative at the module level remains an overwhelming challenge, which may account for the seemingly biased distribution of T1PKSs in fungi and bacteria: small iterative monomodular T1PKSs that are responsible for the enormously diverse fungal natural products exist almost exclusively in fungi. Here we report the discovery of iterative T1PKSs that are unexpectedly both abundant and widespread in Streptomyces. Seven of 11 systematically selected T1PKS monomodules from monomodular T1PKS biosynthetic gene clusters (BGCs) were experimentally confirmed to be iteratively acting, synthesizing diverse branched/nonbranched linear intermediates, and two of them produced bioactive allenic polyketides and citreodiols as end products, respectively. This study indicates the huge potential of iterative T1PKS BGCs from streptomycetes in the discovery of novel polyketides.

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Dove, Alan. "Unlocking polyketides." Nature Biotechnology 19, no. 4 (April 2001): 319. http://dx.doi.org/10.1038/86693.

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Mhlanga, Musa M. "Plant polyketides." Nature Biotechnology 17, no. 1 (January 1999): 9. http://dx.doi.org/10.1038/5350.

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Hua, Yi, Rui Pan, Xuelian Bai, Bin Wei, Jianwei Chen, Hong Wang, and Huawei Zhang. "Aromatic Polyketides from a Symbiotic Strain Aspergillus fumigatus D and Characterization of Their Biosynthetic Gene D8.t287." Marine Drugs 18, no. 6 (June 20, 2020): 324. http://dx.doi.org/10.3390/md18060324.

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The chemical investigation of one symbiotic strain, Aspergillus fumigatus D, from the coastal plant Edgeworthia chrysantha Lindl led to the isolation of eight compounds (1–8), which were respectively identified as rubrofusarin B (1), alternariol 9-O-methyl ether (2), fonsecinone D (3), asperpyrone A (4), asperpyrone D (5), fonsecinone B (6), fonsecinone A (7), and aurasperone A (8) by a combination of spectroscopic methods (1D NMR and ESI-MS) as well as by comparison with the literature data. An antimicrobial assay showed that these aromatic polyketides exhibited no remarkable inhibitory effect on Escherichia coli, Staphyloccocus aureus and Candida albicans. The genomic feature of strain D was analyzed, as well as its biosynthetic gene clusters, using antibiotics and Secondary Metabolite Analysis Shell 5.1.2 (antiSMASH). Plausible biosynthetic pathways for dimeric naphtho-γ-pyrones 3–8 were first proposed in this work. A non-reducing polyketide synthase (PKS) gene D8.t287 responsible for the biosynthesis of these aromatic polyketides 1–8 was identified and characterized by target gene knockout experiment and UPLC-MS analysis.

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Journal articles on the topic 'Polyketides'

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