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      Metabolomics and health: from nutritional crops and plant-based pharmaceuticals to profiling of human biofluids

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          Abstract

          During the past decade metabolomics has emerged as one of the fastest developing branches of “-omics” technologies. Metabolomics involves documentation, identification, and quantification of metabolites through modern analytical platforms in various biological systems. Advanced analytical tools, such as gas chromatography–mass spectrometry (GC/MS), liquid chromatography–mass spectroscopy (LC/MS), and non-destructive nuclear magnetic resonance (NMR) spectroscopy, have facilitated metabolite profiling of complex biological matrices. Metabolomics, along with transcriptomics, has an influential role in discovering connections between genetic regulation, metabolite phenotyping and biomarkers identification. Comprehensive metabolite profiling allows integration of the summarized data towards manipulation of biosynthetic pathways, determination of nutritional quality markers, improvement in crop yield, selection of desired metabolites/genes, and their heritability in modern breeding. Along with that, metabolomics is invaluable in predicting the biological activity of medicinal plants, assisting the bioactivity-guided fractionation process and bioactive leads discovery, as well as serving as a tool for quality control and authentication of commercial plant-derived natural products. Metabolomic analysis of human biofluids is implemented in clinical practice to discriminate between physiological and pathological state in humans, to aid early disease biomarker discovery and predict individual response to drug therapy. Thus, metabolomics could be utilized to preserve human health by improving the nutritional quality of crops and accelerating plant-derived bioactive leads discovery through disease diagnostics, or through increasing the therapeutic efficacy of drugs via more personalized approach. Here, we attempt to explore the potential value of metabolite profiling comprising the above-mentioned applications of metabolomics in crop improvement, medicinal plants utilization, and, in the prognosis, diagnosis and management of complex diseases.

          Supplementary Information

          The online version contains supplementary material available at 10.1007/s00018-021-03918-3.

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          Most cited references109

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          Natural products in drug discovery: advances and opportunities

          Natural products and their structural analogues have historically made a major contribution to pharmacotherapy, especially for cancer and infectious diseases. Nevertheless, natural products also present challenges for drug discovery, such as technical barriers to screening, isolation, characterization and optimization, which contributed to a decline in their pursuit by the pharmaceutical industry from the 1990s onwards. In recent years, several technological and scientific developments — including improved analytical tools, genome mining and engineering strategies, and microbial culturing advances — are addressing such challenges and opening up new opportunities. Consequently, interest in natural products as drug leads is being revitalized, particularly for tackling antimicrobial resistance. Here, we summarize recent technological developments that are enabling natural product-based drug discovery, highlight selected applications and discuss key opportunities.
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            Rewiring of the Fruit Metabolome in Tomato Breeding

            Humans heavily rely on dozens of domesticated plant species that have been further improved through intensive breeding. To evaluate how breeding changed the tomato fruit metabolome, we have generated and analyzed a dataset encompassing genomes, transcriptomes, and metabolomes from hundreds of tomato genotypes. The combined results illustrate how breeding globally altered fruit metabolite content. Selection for alleles of genes associated with larger fruits altered metabolite profiles as a consequence of linkage with nearby genes. Selection of five major loci reduced the accumulation of anti-nutritional steroidal glycoalkaloids in ripened fruits, rendering the fruit more edible. Breeding for pink tomatoes modified the content of over 100 metabolites. The introgression of resistance genes from wild relatives in cultivars also resulted in major and unexpected metabolic changes. The study reveals a multi-omics view of the metabolic breeding history of tomato, as well as provides insights into metabolome-assisted breeding and plant biology.
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              The use of metabolomics to dissect plant responses to abiotic stresses

              Plant metabolism is perturbed by various abiotic stresses. As such the metabolic network of plants must be reconfigured under stress conditions in order to allow both the maintenance of metabolic homeostasis and the production of compounds that ameliorate the stress. The recent development and adoption of metabolomics and systems biology approaches enable us not only to gain a comprehensive overview, but also a detailed analysis of crucial components of the plant metabolic response to abiotic stresses. In this review we introduce the analytical methods used for plant metabolomics and describe their use in studies related to the metabolic response to water, temperature, light, nutrient limitation, ion and oxidative stresses. Both similarity and specificity of the metabolic responses against diverse abiotic stress are evaluated using data available in the literature. Classically discussed stress compounds such as proline, γ-amino butyrate and polyamines are reviewed, and the widespread importance of branched chain amino acid metabolism under stress condition is discussed. Finally, where possible, mechanistic insights into metabolic regulatory processes are discussed. Electronic supplementary material The online version of this article (doi:10.1007/s00018-012-1091-5) contains supplementary material, which is available to authorized users.
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                Author and article information

                Contributors
                milengeorgiev@gbg.bg
                Journal
                Cell Mol Life Sci
                Cell Mol Life Sci
                Cellular and Molecular Life Sciences
                Springer International Publishing (Cham )
                1420-682X
                1420-9071
                19 August 2021
                19 August 2021
                2021
                : 78
                : 19-20
                : 6487-6503
                Affiliations
                [1 ]GRID grid.510916.a, ISNI 0000 0004 9334 5103, Department Plant Cell Biotechnology, , Center of Plant Systems Biology and Biotechnology, ; 4000 Plovdiv, Bulgaria
                [2 ]GRID grid.410344.6, ISNI 0000 0001 2097 3094, Laboratory of Metabolomics, Department of Biotechnology, The Stephan Angeloff Institute of Microbiology, , Bulgarian Academy of Sciences, ; 4000 Plovdiv, Bulgaria
                Author information
                http://orcid.org/0000-0001-5248-6135
                Article
                3918
                10.1007/s00018-021-03918-3
                8558153
                34410445
                0f18ce63-0f9e-420f-9aef-17a1c6d59adb
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 2 April 2021
                : 5 August 2021
                : 10 August 2021
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100010684, H2020 Spreading Excellence and Widening Participation;
                Award ID: PlantaSYST-739582
                Award Recipient :
                Categories
                Review
                Custom metadata
                © Springer Nature Switzerland AG 2021

                Molecular biology
                metabolomics,crops,medicinal plants,biofluids,biomarkers
                Molecular biology
                metabolomics, crops, medicinal plants, biofluids, biomarkers

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