Microbial Bioactives
Unveiling the Ocean’s Chemical Wealth: A Systematic Exploration of Marine Microbiome Secondary Metabolites Through Genome Mining, Metagenomics, and Yield Enhancement Strategies
Ali Korhan Sig 1*, El-Sayed Abdel-Malek El-Sheikh 2, Leyla Acik 3
Microbial Bioactives 6 (1) 1-8 https://doi.org/10.25163/microbbioacts.6110669
Submitted: 11 December 2022 Revised: 04 February 2023 Accepted: 14 February 2023 Published: 16 February 2023
Abstract
Marine microbiomes represent one of the most promising yet underexplored reservoirs of chemical diversity for drug discovery. This systematic review and meta-analysis synthesize evidence on the discovery, biosynthetic logic, and yield optimization of secondary metabolites derived from marine microorganisms, with particular emphasis on nonribosomal peptides (NRPs) and polyketides (PKs). Owing to the “great plate count anomaly,” where approximately 99% of marine microbes remain unculturable, conventional screening approaches have proven insufficient to capture this diversity. Consequently, modern strategies such as genome mining, metagenomics, and synthetic biology have transformed marine biodiscovery into a data-driven discipline. We systematically examine how biosynthetic gene clusters (BGCs) encoding NRPS and PKS systems are identified using computational tools, including antiSMASH and PRISM, and how metagenomic approaches enable access to complex microbial consortia inhabiting sponges, tunicates, and sediments. Quantitative synthesis of reported studies further highlights the effectiveness of yield enhancement strategies—such as elicitation, co-cultivation, mutagenesis, and pathway refactoring—in improving production of high-value compounds like Taxol from fungal endophytes. Evolutionary mechanisms, including horizontal gene transfer and modular rearrangement, are discussed as key drivers of chemical innovation in marine microbes. Collectively, the findings demonstrate that integrating genomics, metabolomics, and experimental optimization not only accelerates the identification of novel bioactive scaffolds but also addresses long-standing challenges in sustainable production. This review underscores the critical role of marine microbiomes in expanding the natural product pipeline and provides a consolidated framework to guide future translational research and pharmaceutical development.
Keywords: Marine microbiomes; secondary metabolites; genome mining; metagenomics; nonribosomal peptides; polyketides; biosynthetic gene clusters; natural product discovery; yield enhancement; synthetic biology
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