From Genes to Medicines: Unraveling the Biosynthesis and Biogenesis of Secondary Metabolites
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2026
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| _version_ | 1866901469148479488 |
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| author | natural product chemistry |
| author_facet | natural product chemistry |
| contents | Secondary metabolites are specialized, low-molecular-weight organic compounds produced by plants and microorganisms. While not strictly essential for basic growth, they play indispensable ecological roles in defense, environmental adaptation, and symbiotic signaling. Because of their immense structural diversity and potent biological activities, these compounds are highly valued in medicine, agriculture, and industry. This extensive review details the fundamental biochemical routes responsible for their creation, including the shikimic acid, mevalonate/methylerythritol phosphate, and acetate-malonate pathways. It also explores the complex molecular assembly lines governed by polyketide synthases (PKS), nonribosomal peptide synthetases (NRPS), and terpene cyclases that generate vast chemical diversity. A major bottleneck in natural product discovery is that many biosynthetic gene clusters (BGCs) remain silent or unexpressed under standard laboratory conditions, and native plants often produce these compounds in minute quantities. To address these hurdles, the article outlines a suite of advanced research methodologies. Genome mining, powered by bioinformatics tools like antiSMASH and reference databases like MIBiG, enables the in silico prediction and genetic dereplication of BGCs, allowing researchers to prioritize novel pathways and avoid redundant discoveries. Furthermore, multi-omics integration (genomics, transcriptomics, metabolomics) and machine learning algorithms facilitate the de novo prediction of metabolic networks and bioactivity. To translate these genetic blueprints into viable clinical candidates, researchers employ synthetic biology and metabolic engineering. Techniques such as heterologous expression in optimized prokaryotic or fungal chassis allow for scalable production. Additionally, non-genetic strategies like the One Strain Many Compounds (OSMAC) approach, microbial co-cultivation, and chemical elicitation in plant cell cultures mimic natural ecological stressors to successfully activate cryptic BGCs and dramatically enhance metabolite yields. By bridging the gap between genomic potential and chemical reality, these integrated approaches provide a robust framework for accelerating the discovery and sustainable production of next-generation therapeutics. Source: https://www.natprodchem.com/posts/from-genes-to-medicines-unraveling-the-biosynthesis-and-biogenesis-of-secondary-metabolites |
| format | Recurso digital |
| id | zenodo_https___doi_org_10_5281_zenodo_19658985 |
| institution | Zenodo |
| language | eng |
| publishDate | 2026 |
| publisher | Zenodo |
| record_format | zenodo |
| spellingShingle | From Genes to Medicines: Unraveling the Biosynthesis and Biogenesis of Secondary Metabolites natural product chemistry secondary metabolites biosynthesis genome mining metabolic engineering biosynthetic gene clusters multi-omics polyketide synthases elicitation Secondary metabolites are specialized, low-molecular-weight organic compounds produced by plants and microorganisms. While not strictly essential for basic growth, they play indispensable ecological roles in defense, environmental adaptation, and symbiotic signaling. Because of their immense structural diversity and potent biological activities, these compounds are highly valued in medicine, agriculture, and industry. This extensive review details the fundamental biochemical routes responsible for their creation, including the shikimic acid, mevalonate/methylerythritol phosphate, and acetate-malonate pathways. It also explores the complex molecular assembly lines governed by polyketide synthases (PKS), nonribosomal peptide synthetases (NRPS), and terpene cyclases that generate vast chemical diversity. A major bottleneck in natural product discovery is that many biosynthetic gene clusters (BGCs) remain silent or unexpressed under standard laboratory conditions, and native plants often produce these compounds in minute quantities. To address these hurdles, the article outlines a suite of advanced research methodologies. Genome mining, powered by bioinformatics tools like antiSMASH and reference databases like MIBiG, enables the in silico prediction and genetic dereplication of BGCs, allowing researchers to prioritize novel pathways and avoid redundant discoveries. Furthermore, multi-omics integration (genomics, transcriptomics, metabolomics) and machine learning algorithms facilitate the de novo prediction of metabolic networks and bioactivity. To translate these genetic blueprints into viable clinical candidates, researchers employ synthetic biology and metabolic engineering. Techniques such as heterologous expression in optimized prokaryotic or fungal chassis allow for scalable production. Additionally, non-genetic strategies like the One Strain Many Compounds (OSMAC) approach, microbial co-cultivation, and chemical elicitation in plant cell cultures mimic natural ecological stressors to successfully activate cryptic BGCs and dramatically enhance metabolite yields. By bridging the gap between genomic potential and chemical reality, these integrated approaches provide a robust framework for accelerating the discovery and sustainable production of next-generation therapeutics. Source: https://www.natprodchem.com/posts/from-genes-to-medicines-unraveling-the-biosynthesis-and-biogenesis-of-secondary-metabolites |
| title | From Genes to Medicines: Unraveling the Biosynthesis and Biogenesis of Secondary Metabolites |
| topic | secondary metabolites biosynthesis genome mining metabolic engineering biosynthetic gene clusters multi-omics polyketide synthases elicitation |
| url | https://doi.org/10.5281/zenodo.19658985 |