Microbial Bioactives
Microbial Bioactives | Online ISSN 2209-2161
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Volume 9 Number 1 2026
REVIEWS (Open Access)
Unlocking the Silent Biosynthetic Wealth of Marine Microbiomes: A Systematic Review and Meta-Analysis of NRPS and Polyketide Discovery Strategies
Mitul Bhuptani 1, Vijay Jagdish Upadhye 1, Ramji Gupta 2, Adesh Kolapkar 3
Microbial Bioactives 9 (1) 1-8 https://doi.org/10.25163/microbbioacts.9110614
Submitted: 10 November 2025 Revised: 25 January 2026 Accepted: 05 February 2026 Published: 07 February 2026
Abstract
Marine microbiomes have emerged as a vast and largely untapped reservoir of structurally diverse secondary metabolites with significant pharmaceutical potential. However, despite rapid advances in genome mining and metagenomics, the extent to which marine microbial communities consistently enhance natural product discovery has not been systematically quantified. This systematic review and meta-analysis critically evaluate discovery strategies targeting nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) biosynthetic systems within marine microbiomes. A comprehensive search across major databases identified studies employing culture-dependent screening, genome mining, metagenomic surveys, and integrative multi-omic approaches. Eligible studies reporting quantifiable measures of biosynthetic gene cluster (BGC) abundance, diversity, or experimentally validated metabolite detection were included in a random-effects meta-analysis to account for ecological and methodological heterogeneity. Effect sizes were calculated from reported discovery outcomes and synthesized using established meta-analytic frameworks. The pooled analysis revealed a statistically significant positive association between marine microbiome exploration and enhanced secondary metabolite discovery. Genome-enabled and symbiosis-focused investigations consistently produced larger effect sizes than traditional cultivation-based methods. Substantial heterogeneity was observed, reflecting genuine biological variation across marine habitats, taxa, and analytical pipelines rather than analytical instability. Funnel plot evaluation suggested mild asymmetry but did not indicate strong evidence of systematic publication bias. Collectively, the findings provide quantitative confirmation that marine microbiomes represent a reliable and underexploited source of biosynthetic innovation. The results emphasize the strategic importance of genome mining, metagenomics, and multi-omic integration for unlocking cryptic metabolic pathways and support prioritizing marine microbial systems in future natural product and drug discovery pipelines.
Keywords: Marine microbiome; secondary metabolites; natural products; genome mining; metagenomics; biosynthetic gene clusters; systematic review; meta-analysis
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