Littérature scientifique sur le sujet « Specialized metabolome »

Cyanobacteria are known to produce a large diversity of specialized metabolites that can cause severe (eco)toxicological effects. In the lagoon of Tahiti, the benthic cyanobacterium Leibleinia gracilis is commonly found overgrowing the proliferative macroalga Turbinaria ornata or dead branching corals. The specialized metabolome of the cyanobacterium L. gracilis was therefore investigated together with its variability on both substrates and changes in environmental parameters. For the study of the metabolome variability, replicates of L. gracilis were collected in the same location of the lagoon of Tahiti before and after a raining event, both on dead corals and on T. ornata. The variability in the metabolome was inferred from a comparative non-targeted metabolomic using high resolution mass spectrometry (MS) data and a molecular network analysis built through MS/MS analyses. Oxidized fatty acid derivatives including the unusual 11-oxopalmitelaidic acid were found as major constituents of the specialized metabolome of this species. Significant variations in the metabolome of the cyanobacteria were observed, being more important with a change in environmental factors. Erucamide was found to be the main chemical marker highly present when the cyanobacterium grows on the macroalga. This study highlights the importance of combined approaches in metabolomics and molecular networks to inspect the variability in the metabolome of cyanobacteria with applications for ecological questions.

Plants show an extraordinary diversity in chemical composition and are characterized by different functional traits. However, relationships between the foliar primary and specialized metabolism in terms of metabolite numbers and composition as well as links with the leaf economics spectrum have rarely been explored. We investigated these relationships in leaves of 20 woody species from the Mediterranean region grown as saplings in a common garden, using a comparative ecometabolomics approach that included (semi-)polar primary and specialized metabolites. Our analyses revealed significant positive correlations between both the numbers and relative composition of primary and specialized metabolites. The leaf metabolomes were highly species-specific but in addition showed some phylogenetic imprints. Moreover, metabolomes of deciduous species were distinct from those of evergreens. Significant relationships were found between the primary metabolome and nitrogen content and carbon/nitrogen ratio, important traits of the leaf economics spectrum, ranging from acquisitive (mostly deciduous) to conservative (evergreen) leaves. A comprehensive understanding of various leaf traits and their coordination in different plant species may facilitate our understanding of plant functioning in ecosystems. Chemodiversity is thereby an important component of biodiversity.

Mallotus japonicus is a valuable traditional medicinal plant in East Asia for applications as a gastrointestinal drug. However, the molecular components involved in the biosynthesis of bioactive metabolites have not yet been explored, primarily due to a lack of omics resources. In this study, we established metabolome and transcriptome resources for M. japonicus to capture the diverse metabolite constituents and active transcripts involved in its biosynthesis and regulation. A combination of untargeted metabolite profiling with data-dependent metabolite fragmentation and metabolite annotation through manual curation and feature-based molecular networking established an overall metabospace of M. japonicus represented by 2129 metabolite features. M. japonicus de novo transcriptome assembly showed 96.9% transcriptome completeness, representing 226,250 active transcripts across seven tissues. We identified specialized metabolites biosynthesis in a tissue-specific manner, with a strong correlation between transcripts expression and metabolite accumulations in M. japonicus. The correlation- and network-based integration of metabolome and transcriptome datasets identified candidate genes involved in the biosynthesis of key specialized metabolites of M. japonicus. We further used phylogenetic analysis to identify 13 C-glycosyltransferases and 11 methyltransferases coding candidate genes involved in the biosynthesis of medicinally important bergenin. This study provides comprehensive, high-quality multi-omics resources to further investigate biological properties of specialized metabolites biosynthesis in M. japonicus.

Different plant defense theories have provided important theoretical guidance in explaining patterns in plant specialized metabolism, but their critical predictions remain to be tested. Here, we systematically explored the metabolomes of Nicotiana attenuata, from single plants to populations, as well as of closely related species, using unbiased tandem mass spectrometry (MS/MS) analyses and processed the abundances of compound spectrum–based MS features within an information theory framework to test critical predictions of optimal defense (OD) and moving target (MT) theories. Information components of plant metabolomes were consistent with the OD theory but contradicted the main prediction of the MT theory for herbivory-induced dynamics of metabolome compositions. From micro- to macroevolutionary scales, jasmonate signaling was confirmed as the master determinant of OD, while ethylene signaling provided fine-tuning for herbivore-specific responses annotated via MS/MS molecular networks.

Abstract Emerging metabolomic tools can now be used to establish metabolic signatures of specialized circulating hematopoietic cells in physiologic or pathologic conditions and in human hematologic diseases. To determine metabolomes of normal and sickle cell erythrocytes, we used an extraction method of erythrocytes metabolites coupled with a liquid chromatography-mass spectrometry–based metabolite profiling method. Comparison of these 2 metabolomes identified major changes in metabolites produced by (1) endogenous glycolysis characterized by accumulation of many glycolytic intermediates; (2) endogenous glutathione and ascorbate metabolisms characterized by accumulation of ascorbate metabolism intermediates, such as diketogulonic acid and decreased levels of both glutathione and glutathione disulfide; (3) membrane turnover, such as carnitine, or membrane transport characteristics, such as amino acids; and (4) exogenous arginine and NO metabolisms, such as spermine, spermidine, or citrulline. Finally, metabolomic analysis of young and old normal red blood cells indicates metabolites whose levels are directly related to sickle cell disease. These results show the relevance of metabolic profiling for the follow-up of sickle cell patients or other red blood cell diseases and pinpoint the importance of metabolomics to further depict the pathophysiology of human hematologic diseases.

Streptomyces cyanogenus S136 is known to produce landomycin family antibiotics, particularly its largest congener, landomycin A. Except for landomycins and polyene lucensomycin, no other specialized metabolites were sourced from S136. Nevertheless, S136 genome sequencing revealed over 40 biosynthetic gene clusters (BGCs), implying underappreciated potential of this strain for the production of novel bioactive natural compounds. We set out to gain deeper insight into the specialized metabolome of this strain. First, trans­criptomic analysis of S136 grown under landomycin production conditions has been carried out, revealing that most of them are expressed at a basal level. This, likely, leads to a phenotypic silence of most of the BGCs. Nevertheless, several notable exceptions have been spotted. First of all, landomycin BGC is expressed at high level (at least 100 Transcripts Per Million mapped reads (TPM); and around 1000 TPM for minimal polyketide synthase genes lanFABC). Similarly, high levels of expression showed BGCs # 2, 4, 7 and 33, of which #2, encoding unknown saccharide, is the most dissimilar to the described precedents. RNAseq data also allowed us to delineate better the borders of several presumed BGCs. In the next phase of the work we singled out a few BGCs within S136 that appeared to be promising. First, these BGCs exhibited low similarity to the other gene clusters directing the production of known natural products. Second, the BGCs harbored cluster-situated regulatory genes that can be employed in the attempts to activate the expression of cryptic pathways. For one such BGC we constructed two plasmids for expression of several such regulatory genes and introduced them into S136 and its derivative deficient in production of landomycin A. Bioassays showed no differences in bioactivity of the recombinant strains as compared to the initial strains. Liquid chromatography coupled to mass spectrometry (LC-MS) analysis of several S. cyanogenus samples revealed the effects of genotype, growth conditions and extraction on specialized metabolome of this species, setting reference point for further stu­dies.

Specialized metabolites are produced via discrete metabolic pathways. These small molecules play significant roles in plant growth and development, as well as defense against environmental stresses. These include damping off or seedling blight at a post-emergence stage. Targeted metabolomics was followed to gain insights into metabolome changes characteristic of different developmental stages of sorghum seedlings. Metabolites were extracted from leaves at seven time points post-germination and analyzed using ultra-high performance liquid chromatography coupled to mass spectrometry. Multivariate statistical analysis combined with chemometric tools, such as principal component analysis, hierarchical clustering analysis, and orthogonal partial least squares–discriminant analysis, were applied for data exploration and to reduce data dimensionality as well as for the selection of potential discriminant biomarkers. Changes in metabolome patterns of the seedlings were analyzed in the early, middle, and late stages of growth (7, 14, and 29 days post-germination). The metabolite classes were amino acids, organic acids, lipids, cyanogenic glycosides, hormones, hydroxycinnamic acid derivatives, and flavonoids, with the latter representing the largest class of metabolites. In general, the metabolite content showed an increase with the progression of the plant growth stages. Most of the differential metabolites were derived from tryptophan and phenylalanine, which contribute to innate immune defenses as well as growth. Quantitative analysis identified a correlation of apigenin flavone derivatives with growth stage. Data-driven investigations of these metabolomes provided new insights into the developmental dynamics that occur in seedlings to limit post-germination mortality.

Several main families of Ranunculales are rich in alkaloids and other medicinal compounds; many species of these families are used in traditional and folk medicine. Dichocarpum is a representative medicinal genus of Ranunculaceae, but the genetic basis of its metabolic phenotype has not been investigated, which hinders its sustainable conservation and utilization. We use the third-generation high-throughput sequencing and metabolomic techniques to decipher the full-length transcriptomes and metabolomes of five Dichocarpum species endemic in China, and 71,598 non-redundant full-length transcripts were obtained, many of which are involved in defense, stress response and immunity, especially those participating in the biosynthesis of specialized metabolites such as benzylisoquinoline alkaloids (BIAs). Twenty-seven orthologs extracted from trancriptome datasets were concatenated to reconstruct the phylogenetic tree, which was verified by the clustering analysis based on the metabolomic profile and agreed with the Pearson correlation between gene expression patterns of Dichocarpum species. The phylogenomic analysis of phytometabolite biosynthesis genes, e.g., (S)-norcoclaurine synthase, methyltransferases, cytochrome p450 monooxygenases, berberine bridge enzyme and (S)-tetrahydroprotoberberine oxidase, revealed the evolutionary trajectories leading to the chemodiversity, especially that of protoberberine type, aporphine type and bis-BIA abundant in Dichocarpum and related genera. The biosynthesis pathways of these BIAs are proposed based on full-length transcriptomes and metabolomes of Dichocarpum. Within Ranunculales, the gene duplications are common, and a unique whole genome duplication is possible in Dichocarpum. The extensive correlations between metabolite content and gene expression support the co-evolution of various genes essential for the production of different specialized metabolites. Our study provides insights into the transcriptomic and metabolomic landscapes of Dichocarpum, which will assist further studies on genomics and application of Ranunculales plants.

Brachypodium distachyon, because of its fully sequenced genome, is frequently used as a model grass species. However, its metabolome, which constitutes an indispensable element of complex biological systems, remains poorly characterized. In this study, we conducted comprehensive, liquid chromatography-mass spectrometry (LC-MS)-based metabolomic examination of roots, leaves and spikes of Brachypodium Bd21 and Bd3-1 lines. Our pathway enrichment analysis emphasised the accumulation of specialized metabolites representing the flavonoid biosynthetic pathway in parallel with processes related to nucleotide, sugar and amino acid metabolism. Similarities in metabolite profiles between both lines were relatively high in roots and leaves while spikes showed higher metabolic variance within both accessions. In roots, differences between Bd21 and Bd3-1 lines were manifested primarily in diterpenoid metabolism, while differences within spikes and leaves concerned nucleotide metabolism and nitrogen management. Additionally, sulphate-containing metabolites differentiated Bd21 and Bd3-1 lines in spikes. Structural analysis based on MS fragmentation spectra enabled identification of 93 specialized metabolites. Among them phenylpropanoids and flavonoids derivatives were mainly determined. As compared with closely related barley and wheat species, metabolic profile of Brachypodium is characterized with presence of threonate derivatives of hydroxycinnamic acids.

Les métabolites spécialisés (MS) jouent un rôle crucial dans l'interaction des plantes et des graines avec leur environnement. De plus, les modifications des MS contribuent largement à leur(s) diversité et activités. Malgré leur importance pour la qualité des graines, l'étude des effets de l'environnement sur la production et l'accumulation de ces MS a été négligée. Les graines accumulent à la fois des MS bénéfiques et toxiques, qui jouent divers rôles biologiques et écologiques, et sont importants dans la nutrition animale et humaine et pour d'autres usages industriels. Ainsi, l'étude de la composition et distribution des MS dans les graines sous l'influence de stress environnementaux est d'une importance majeure, particulièrement dans le contexte actuel de changement climatique. Les Brassicacées incluent des espèces modèles et cultivées largement répandues et utilisées à de fins multiples. Leurs graines présentent une grande diversité de composition en MS, ce qui en fait des modèles d'étude intéressants. Ce projet de thèse visait à caractériser la diversité et la plasticité du métabolome spécialisé des graines de Brassicacées sous l'influence de stress environnementaux, en utilisant des approches multi-omiques, de biologie moléculaire et de génétique inverse. Dans une première étude, la diversité et la plasticité des MS des graines de plusieurs génotypes de Camelina sativa cultivés en plein champ plusieurs années consécutives ont été évaluées. Les résultats obtenus montrent que l'accumulation des MS des graines de Camelina est plus impactée par les conditions environnementales que par le génotype, et que la plasticité des MS est plus élevée que celle des principaux composés de réserve des graines. Une deuxième étude avait pour but d'évaluer l'effet de conditions de stress sur les MS pendant le développement de la graine de l'espèce modèle Arabidopsis thaliana. Dans une étude préliminaire, il a été observé que le stress thermique (ST) induit des différences plus marquées dans le métabolome spécialisé des graines que le stress hydrique ou le chlorure de cuivre (induisant un stress oxydatif et mimant les effets de stress biotiques). Ainsi, l'étude s'est focalisée sur l'effet du ST sur le métabolome spécialisé au cours du développement des graines d'Arabidopsis en utilisant des analyses multi-omiques (analyses métabolomiques et transcriptomiques). Un large panel de MS et de gènes a été affecté par le ST pendant le développement des graines. Plusieurs glucosinolates (GSL) associés à l'hydroxylase ALKENYL HYDROXALKYL PRODUCING 3 (AOP3) étaient fortement induits par le ST. De plus, divers GSL sinapoylés et benzoylés au niveau du thioglucose ont été décrits pour la première fois. Des analyses métabolomiques et physiologiques ont été réalisées sur plusieurs mutants de la biosynthèse des GSL et le génotype sauvage d'Arabidopsis afin de comprendre la régulation de la synthèse, des modifications et les fonctions de ces GSL acylés au thioglucose. Les résultats obtenus montrent que les enzymes SERINE CARBOXYPEPTIDASE LIKE 17 (SCPL17) et BENZOYLGLUCOSINOLATE 1 (BZO1) sont impliquées dans la sinapoylation et/ou la benzoylation du thioglucose des GSL et que ces GSL acylés sont impliqués dans la réponse au ST chez Arabidopsis. Enfin, des analyses multi-omiques ont été réalisées sur les embryons (E) et téguments et albumens (TA) des graines de C. sativa pendant leur développement et germination. Les données obtenues concernant la distribution des GSL dans les graines de C. sativa, A. thaliana et Brassica napus apportent des informations complémentaires aux travaux précédemment décrits sur les fonctions et activités des GSL. Parmi ces espèces de Brassicacées, les GSL dérivés de la méthionine à courte chaîne (<8C) sont accumulés dans les E tandis que les GSL dérivés de la méthionine à longue chaîne (>7C) sont accumulés dans les TA. Les produits de dégradation des GSL présentent des profils d'accumulation divers entre les trois espèces
Specialized metabolites (SMs) play crucial roles in the interaction of plants and seeds with their environment. SM modifications greatly contribute to SM diversity and activities. Despite their importance for seed quality, the study of the impact of the environment on the synthesis, modification and accumulation of SMs in seeds has been neglected. Seeds accumulate both beneficial and antinutritional SMs with a large range of biological and ecological roles and significant importance for human and animal nutrition, and other industrial uses. Hence, study the diversity, distribution and regulation of SMs in seeds upon environmental stresses is of major relevance, especially in the current context of climate change. This is particularly true for seeds of Brassicaceae species, which include both model and crop species that are widely cultivated across the world and used/consumed as vegetables, fodder, or oilseeds. These species show diverse SM composition and distribution, which makes them valuable models to study the impacts of environmental stresses on seed SMs. This Ph.D. project aimed at characterizing the diversity and plasticity of seed specialized metabolites in Brassicaceae species under environmental stresses by using multi-omic, molecular biology and reverse genetic approaches. In a first study, the diversity and plasticity of seed SMs from several Camelina sativa genotypes cultivated in open field for several consecutive years were assessed. The results obtained showed that the accumulation of SMs in Camelina seeds was more impacted by the environmental conditions rather than the genotype, and that the plasticity of SMs was higher compared to those of major seed storage compounds, including oil, proteins, and other primary metabolites. A second study aimed to evaluate the impact of stress conditions on developing seeds of the model species Arabidopsis thaliana. Heat stress (HS) was found to induce the strongest changes in seed specialized metabolome, compared to drought stress and copper chloride stress (inducing oxidative stress and mimicking biotic stress effects). Hence, the study has been focused on studying the effect of HS on specialized metabolome during Arabidopsis seed development by using multi-omic analyses (untargeted metabolomic and transcriptomic analyses). A wide range of SMs and genes were affected by HS during seed development. Among them, glucosinolates (GSLs) related to ALKENYL HYDROXALKYL PRODUCING 3 (AOP3) GSL hydroxylase enzyme were strongly induced by HS. Besides, several thioglucose sinapoylated and benzoylated GSLs were identified and reported for the first time. Untargeted metabolomic and physiological analyses were performed with several Arabidopsis mutants for GSL-related genes and wild-type genotype, in order to elucidate the synthesis, modifications, regulation and functions of those thioglucose acylated GSLs. The obtained results showed that the acyltransferase SERINE CARBOXYPEPTIDASE LIKE 17 (SCPL17) and BENZOYLGLUCOSINOLATE 1 (BZO1) are involved in the sinapoylation and/or benzoylation of GSL thioglucose moieties and that thioglucose benzoylated and sinapoylated GSLs are involved in Arabidopsis HS responses in seeds. Finally, to study and characterize seed SM distribution, multi-omic analyses have been performed on C. sativa seed embryo (SE) and seed coat and endosperm (SCE) tissues from developing and germinating seeds. The data obtained revealed some specific accumulation pattern of GSLs and related degradation products in the different seed tissues of C. sativa, A. thaliana and Brassica napus species that provide valuable complementary information to the previously described work about GSL functions and activities. In particular, the short methionine derived (Met-de) GSLs (<8C) accumulated in SE, while longer Met-de GSLs (>7C) accumulated in SC. Differently, GSL degradation products accumulation showed diverse accumulation patterns in the three Brassicaceae species

Specialized metabolism (secondary metabolism) in glandular trichomes of sweet basil (Ocimum basilicum L.) and accumulation of specialized metabolites (secondary metabolites) in rhizomes of turmeric (Curcuma longa L.) was investigated using proteomic and metabolomic approaches, respectively. In an effort to further clarify the regulation of metabolism in the glandular trichomes of sweet basil, we utilized a proteomics-based approach that applied MudPIT (multidimensional protein identification technology) and GeLC-MS/MS (gel enhanced LC-MS/MS) to protein samples from isolated trichomes of four different basil lines: MC, SW, SD, and EMX-1. Phosphorylation, ubiquitination and methylation of proteins in these samples were detected using X!tandem. Significant differences in distribution of the 755 non-redundant protein entries demonstrated that the proteomes of the glandular trichomes of the four basil lines were quite distinct. Correspondence between proteomic, EST, and metabolic profiling data demonstrated that both transcriptional regulation and post-transcriptional regulation contribute to the chemical diversity. One very interesting finding was that precursors for different classes of terpenoids, including mono- and sesquiterpenoids, appear to be almost exclusively supplied by the MEP (2-C-methyl-D-erythritol 4- phosphate) pathway, but not the mevolonate pathway, in basil glandular trichomes. Our results suggest that carbon flow can be readily redirected between the phenylpropanoid and terpenoid pathways in this specific cell type. To investigate the impact of genetic, developmental and environmental factors on the accumulation of phytochemicals in rhizomes of turmeric, we performed metabolomic analysis in a 2x2x4 full factorial design experiment using GC-MS, LC-MS, and LC-PDA. Our results showed that growth stage had the largest effect on levels of the three major curcuminoids. Co-regulated metabolite modules were detected, which provided valuable information for identification of phytochemicals and investigation of their biosynthesis. Based on LC-MS/MS data, 4 new diarylheptanoids were tentatively identified in turmeric rhizomes using Tandem-MSASC, a home-made software tool that automatically recognizes spectra of unknown compounds using three approaches. Based on our metabolomic results, we proposed two new strategies, “metabolomics-guided discovery” and “correlation bioassay”, to identify bioactive constituents from plant extracts based on information provided by metabolomic investigation.

Le métabolisme spécialisé joue un rôle essentiel dans les interactions plante-environnement. Sa caractérisation chez les plantes cultivées représente un enjeu scientifique important. Au cours de ma thèse, j’ai travaillé à la caractérisation du métabolisme spécialisé et de ses déterminants génétiques chez Brassica napus, et j’ai étudié sa régulation en réponse à l’infection par Leptosphaeria maculans, agent causal du phoma. J’ai contribué au développement d’une méthode de profilage métabolique ciblé et identifié 36 glucosinolates (GLSs) foliaires/racinaires, 32 composés phénoliques (PHLs) foliaires et 18 composés racinaires non documentés jusqu'à présent. La quantification des ces SMs dans 304 accessions de Brassica a permis de révéler des contrastesphytochimiques importants au sein du panel. L’analyse GWAS de ces variations phytochimiques a identifié 104 locus (QTLs). L’architecture génétique ainsi mise en évidence suggère un controle indépendant des sous-catégories de GLSs, PHLs et des nouveaux composés racinaires. Ces travaux fournissent une ressource utile pour l'écologie chimique et la sélection des Brassicas. En utilisant la même méthode de profilage ciblé, nous avons montré une induction des GLSs indoliques 14 jours après inoculation de la tige de B. napus par L. maculans. L'imagerie par spectrométrie de masse de la section transversale de tige de colza infectée a permis de révéler une spatialisation des réponses métaboliques suite à l’infection par L. maculans
Specialized metabolism plays an essential role in plant-environment interactions. Its characterization in cultivated plants represents a significant scientific challenge. During my thesis, I worked on the characterization of the specialized metabolism and its genetic determinants in Brassica napus (oilseed rape), and I studied its regulation in response to infection by Leptosphaeria maculans (causal agent of phoma). I contributed to developing a targeted metabolic profiling method and identified 36 foliar/root glucosinolates (GLSs), 32 foliar phenolic compounds (PHLs), and 18 previously undocumented root compounds. The quantification of these SMs in 304 Brassicaaccessions revealed important phytochemical contrasts within the panel. GWA analysis of these phytochemical variations identified 104 loci (QTLs). The genetic architecture thus highlighted an independent control of the subcategories of GLSs, PHLs, and new root compounds. This work provides a useful resource for Brassica chemical ecology and breeding. Using the same targeted profiling method, we showed induction of indole GLSs 14 days after inoculation of the B. napus stems with L. maculans. Mass spectrometric imaging of the cross-section of infected rapeseed stem revealed the spatialization of metabolic responses to L. maculans infection

Dans cette étude, le palmier Astrocaryum sciophilum a été choisi comme modèle pour l'étude de ses endophytes foliaires. Du fait de sa longévité, nous avons cherché à mettre en évidence une communauté compétitive d’endophytes en fonction de l’âge de ses feuilles. Afin d’évaluer si les métabolites produits par ces endophytes pourraient être utilisés en santé humaine, les extraits de chaque endophyte ont été testés contre Staphylococcus aureus résistant à la méticilline (SARM) ainsi que pour leur activité quorum quenching (QQ). En parallèle, afin d’identifier un rôle écologique de protection de la plante par ces endophytes, des co-cultures ont été réalisées avec le phytopathogène Fusarium oxysporum. Plusieurs extraits de souches ont été sélectionnés afin d’isoler et d’identifier le ou les métabolites responsables des activités biologiques observées. Différents outils analytiques ont permis de guider le processus d’isolement (LC-MS/MS, réseaux moléculaires et imagerie par spectrométrie de masse). L’étude de la communauté d’endophytes isolée des feuilles âgées n’a pas mis en évidence un arsenal chimique plus compétitif. Toutefois, deux souches bactériennes du genre Luteibacter sp. ont montré un extrait actif sur SARM et de nombreux extraits de bactéries présentent une activité QQ. Par la suite, le métabolome secondaire du genre Colletotrichum a été étudié à l’aide des réseaux moléculaires et un champignon de la famille des Xylariaceae a été étudié pour son activité contre F. oxysporum. Dans le cadre de cette thèse, sept souches endophytes ont été étudiées chimiquement permettant l’isolement et l’identification de 42 molécules dont dix sont nouvelles
The palm Astrocaryum sciophilum is the host plant model chosen in this work. Indeed, due to the longevity of its leaves, we expected to highlight a competitive community of endophytes within the oldest leaves. Thus, 197 endophytes have been isolated and identified from different leaves of six palm specimens. In order to evaluate whether the compounds produced by these microorganisms could be used for the treatment of human disease, the ethyl acetate extracts of each endophyte were tested against methicillin-resistant Staphylococcus aureus (MRSA) as well as for a quorum quenching (QQ) activity. Simultaneously, co-culture were carried with the fungi Fusarium oxysporum in order to highlight endophytes providing plant protection against phytopathogens. We selected extracts in order to isolate and identify the bioactive metabolites. Various analytical tools have been used to improve the isolation process (LC-MS/MS, molecular networking or MS imaging).The study of the endophytic community isolated from older leaves did not show a more competitive chemical arsenal. However, two Luteibacter strains exhibited an ethyl acetate extract active against MRSA and several bacteria provide quorum quenching extracts. The metabolome of Colletotrichum genus was studied using molecular networking and a fungus from the Xylariaceae family was studied for its capacity to inhibit F. oxysporum’s growth. In our study, seven endophyte strains were chemically investigated leading to the isolation and identification of 42 molecules whose ten are new

Tryptamine and serotonin are specialized metabolites belonging to the group of tryptophan-derived indolamines that have been demonstrated to be widespread among all the living kingdoms, in which evolution shaped very different distributions and functional versatility. First discovered in humans, these metabolites were later detected in plants in which, despite their wide occurrence in several plant families, the study of their biological roles has been largely neglected. Tryptamine, due to its central position as a precursor of many plant specialized metabolites, including serotonin, has long been considered a mere metabolic intermediate; on the other hand, the increasing awareness of the many medical issues of serotonin (e.g. neurotransmission and hormonal activity), triggered the botanical research towards the elucidation of its biosynthetic pathway and functions also in plants, leading to a huge number of experimental evidences that, yet often controversial, suggest its putative involvement in many different plant physiological processes (e.g. development, stress response and reproduction). This PhD thesis proposed to shed a light on the biological roles of plant tryptamine and serotonin, with a particular focus on an aspect that has never been investigated in plants, i.e. the high level of accumulation of these metabolites within the reproductive organs, such as the fruit, observed in many edible species, which, given the high costs to plant metabolism, can be reasonably hypothesized to reflect an important plant physiological function. To fulfil this aim, this PhD project relied on the use of Solanum lycopersicum, a tryptamine and serotonin accumulator that is a model plant for fruit-bearing crops. The first step consisted in the genetic characterization of the tomato tryptamine and serotonin biosynthetic pathway: a three-member gene family and one single gene codifying for the enzymes of the 2-step pathway that leads to the production of serotonin from tryptophan via tryptamine (i.e. tryptophan decarboxylase, TDC and tryptamine-5-hydroxylase, T5H) were respectively identified and functionally characterized as bona-fide SlTDCs and SlT5H. The expression analysis of these genes and the investigation of tryptamine and serotonin distribution revealed organ and developmental-specific expression and accumulation patterns in tomato, confirming the complementary but not redundant activity of the three SlTDC genes in the plant and the presence of notable amounts of the two indolamines in the fruit, which accumulated with a characteristic trend during development and ripening. Moreover, it was revealed the fruit-specific nature of the SlTDC1 gene that, as a preliminary point in the elucidation of the biological roles of plant tryptamine and serotonin, was targeted by a metabolic engineering approach in order to look for the effects resulting from altered levels of these metabolites on the plant phenotype. Transgenic plants overexpressing this gene resulted in deep modifications of plant metabolome presenting in one case altered morphology of younger leaves. This evidence, together with the observation along the main axis of the wild type plant of complex expression and accumulation gradients of SlTDCs/SlT5H genes and related products, i.e. tryptamine and serotonin, leads to hypothesize the possible interference with the hormonal cross-talk. On the other hand, SlTDC1 knock-out fruits did non exhibit obvious phenotype but further characterization of their metabolome are needed to speculate on the biological roles of tryptamine and serotonin in this organ. In summary, this work provided useful information and details to the biosynthesis, regulation and putative biological roles of plant indolamines in the model plant of tomato and highlighted the putative involvement of the actors of the plant serotonin pathway in important physiological functions, which deserve, thus, future deeper investigation.

Metabolomics is one of the new field of “Omics” approach and the youngest triad of system biology, which provides a broad prospective of how metabolic networks are controlled and indeed emerged as a complementary tool to functional genomics with well-established technologies for genomics, transcriptomics and proteomics. Though, metabolite profiling has been carried out for decades, owing to decisive mechanism of a molecule regulation, the importance of some metabolites in human regimen and their use as diagnostic markers is now being recognized. Plant metabolomics therefore aims to highlight the characterization of metabolite pool of a plant tissue in response to its environment. Seagrassses, a paraphyletic group of marine hydrophilous angiosperms which evolved three to four times from land plants back to the sea. Seagrasses share a number of analogous acquired metabolic adaptations owing to their convergent evolution, but their secondary metabolism varied among the four families that can be considered as true seagrasses. From a chemotaxonomic point of view, numerous specialized metabolites have often been studied in seagrasses. Hence, this chapter focus the metabolome of seagrasses in order to explore their bioactive properties and the recent advancements adopted in analytical technology platforms to study the non-targeted metabolomics of seagrasses using OMICS approach.

Trichomes are specialised epidermal outgrowth that is present on the aerial parts of plants. On the basis of morphological and cellular variation, they are categorized into non-glandular trichomes (NGTs) and glandular trichomes (GTs). NGTs are known to be involved in the protective and defensive roles that attribute to provide structural and chemical corroboration to form specialized groups of secondary metabolites. GTs are specialized micro-organs that are considered factories for the biosynthesis of a considerable amount of different classes of bioactive metabolites. Conventionally these glandular and non-glandular trichomes are known for their protective roles against different biotic and abiotic stresses. Recently, they have attracted the interest of various researchers as a specialized organ for the production of various bioactive molecules of high pharmaceutical and commercial values. The major groups of secondary metabolites such as terpenoids, flavonoids, phenylpropanes, methyl ketones, acyl sugars and defensive proteins are reported in the trichomes of different plant species. However, the conception of the molecular regulation of their biosynthesis, storage and distribution during the development of trichomes is scattered. This review compiles structural and functional aspects of GTs and NGTs along with the molecular mechanism regulated for the production of secondary metabolite in these specialized organs. In addition, the role of several bio-physical parameters that affect the trichome biochemistry, which either directly or indirectly influence the biosynthesis of secondary metabolite, will also be focussed. The systemized knowledge of trichome biology, secondary metabolite pathway modulation and metabolic engineering at one platform will be helpful to explore recent advances in the field of trichome engineering in many medicinally important plants.

Carbohydrates may be categorized into three classes, as monosaccharides, di- and oligosaccharides, and polysaccharides (starches, cellulose, hemicelluloses, pectin, gums and mucilages). Carbohydrates are sources of energy, storage compounds and structural components in plants. Many soluble sugars, known as compatible solutes, accumulate in plants and protect the plant from stress induced cellular disturbances. Many polysaccharides (such as cellulose, hemicellulose, pectin, non-digestible oligosaccharides, gums and mucilages), resistant to human salivary and intestinal enzymes, are considered as dietary fibres. Consumption of dietary fibre improves glycemic index, reduces lipid levels, and exhibits prebiotic effects. A glycoside is a compound formed by conjugation of one or more sugars with a non-carbohydrate metabolite.

Abstract In multicellular organisms, cell signaling through the nervous, immune, and endocrine systems is essential for coordinating metabolic functions among all cells. Signals range from nutrient and metabolite levels in extracellular fluids to specialized systems including chemical messengers, storage and transportation mechanisms, and receptors. Specialized endocrine cells produce chemical messengers (hormones) that interact with receptors in local and distant target cells. There are intimate links between the endocrine and nervous systems such as the hypothalamic–pituitary gland complex in which specialized neurons produce hormones. Depending on the hormone, target cells may be confined to a specific organ or may be more widespread. By binding to receptors and influencing intracellular signaling systems, hormones control many processes at the molecular level during gestation and postnatal life. Major endocrine glands include the pituitary gland, thyroid gland, parathyroid glands, pancreatic islets, adrenal glands, testes, and ovaries. When activated by a hormone, receptors on or in target cells trigger a cascade of intracellular reactions. An agonist is a hormone or chemical that binds to a receptor and induces specific biochemical effects; antagonists compete for binding to a receptor but do not induce the biochemical effects associated with the receptor.

Metabolomics is a fascinating area that specializes in analyzing the small molecules in our frame, like hormones and enzymes, that play an important role in our metabolism. With the aid of reading these molecules, scientists can gain insights into our metabolic fitness and the way our body processes nutrients. It entails different factors such as energy production, nutrient usage, and waste elimination. Through metabolomics, researchers can become aware of precise metabolic biomarkers that imply the state of our fitness. Through studying these markers, they are able to hit upon early symptoms of metabolic disorders like diabetes, obesity, and cardiovascular ailment. This knowledge can then be used to broaden customized interventions and treatments to improve metabolic health. It is able to assist in the development of centered treatment plans, personalized nutrition plans, and preventive strategies. In this chapter, we will attempt towards achieving and maintaining optimal health with the study of metabolomics biomarkers.

Plants are active biochemical factories of a vast group of secondary metabolites (SMs) and these SMs are indeed a basic source of various commercial pharmaceutical drugs. From the prehistoric time, plants have been used for therapeutic resolutions. Medicinal and aromatic plants are the biogenic pond of diverse forms of SMs, which results in their overexploitation. There is an increasing need for the natural phytochemicals from plants for sustainable and economical value forces their mass production through in vitro plant tissue culture (PTC) methods. A vast quantity of medicinal plants and their metabolites have been developed by in vitro culture techniques in a small time period related to conventional methods. In vitro plant cell cultures assist in a potential role in the commercial production of SMs. The novel prime practices of in vitro techniques facilitate transgenic cultures and enlighten the understanding lane of regulation and expression of biosynthetic pathways. SMs have composite chemical alignment and are created in response to different forms of stress to accomplish various physiological tasks in the plant host system. They are immensely utilized in pharmaceutical industries, dietary supplements, cosmetics, fragrances, dyes, flavors, etc. SMs are also termed specialised metabolites, secondary products, toxins or natural products; these are basically organic compounds produced by plants and are not directly involved in the growth and development of the plant. Instead, they usually intervene with ecological interactions and conceivably produce selective support for the plant host by increasing its survivability or productivity. Few SMs are specific for a narrow set of plant species within a phylogenetic group. SMs habitually play a vital role in the defense systems of plants against herbivory and other interspecies defences. Human beings uses SMs mainly for medicines, pigments, flavourings and recreational drugs. Prolonged use of these SMs in several industrial areas still needs to be focused to enhance the fabrication by using in vitro PTC practices and optimizing their largescale fabrication using bioreactors. The present book chapter intends to highlight the rationale of the in vitro production of SMs from medicinal plants and their progress in the modern epoch for the mass production facts toward the step of commercial and economical forte.

The peroxisome is a specialized organelle which employs molecular oxygen in the oxidation of complex organic molecules including lipids. Enzymatic pathways for the metabolism of fatty acids, including very long-chain fatty acids (VLCFAs), enable this organelle to carry out β‎-oxidation in partnership with mitochondria. A peroxisomal pathway for isoprenoid lipids derived from chlorophyll, such as phytanic acid, utilizes α‎-oxidation, but a default mechanism involving ω‎-oxidation may also metabolize phytanic acid and its derivatives. The biochemical manifestations, molecular pathology, and diverse clinical features of many peroxisomal disorders have now been clarified, offering the promise of prompt diagnosis, better management, and useful means to provide appropriate genetic counselling for affected families. At the same time, specific treatments including rigorous dietary interventions and plasmapheresis to remove undegraded toxic metabolites offer credible hope of improvement and prevention of disease in affected individuals. X-linked adrenoleukodystrophy (X-ALD)—due to mutations in the gene for an ATP-binding cassette (ABC) protein of unknown function and characterized by accumulation of unbranched saturated VLCFAs, particularly hexacosanoate (C26), in the cholesterol esters of brain white matter, adrenal cortex, and certain sphingolipids of the brain. The disease has multiple phenotypes. Most cases develop increasing handicap; management is palliative and supportive in most instances. Adult Refsum’s disease—due in most cases to mutations in the gene for phytanoyl-CoA hydroxylase (PHYH) such that patients are unable to detoxify phytanic acid by α‎-oxidation and have greatly elevated levels of this in their plasma. Usually presents in late childhood with progressive deterioration of night vision, the occurrence of progressive retinitis pigmentosa, and anosmia. Treatment is by restriction of dietary phytanic acid, with or without its elimination by plasmapheresis or apheresis.