Biosynthetic Potential of Marine Microbial Communities Revealed Through Metagenomic Insights Into PKS and NRPS Pathways: A Systematic Review and Meta-Analysis

The discovery and development of bioactive compounds remain a cornerstone of pharmaceutical and biotechnological innovation. Microbial biosynthesis, particularly through nonribosomal peptide synthetases (NRPS) and type-I polyketide synthases (PKS), offers a diverse and untapped reservoir of chemical entities with potential antimicrobial, anticancer, and immunomodulatory properties. This systematic review and meta-analysis synthesized evidence from published studies to evaluate the diversity, functional roles, and applications of microbial secondary metabolites. A comprehensive search of databases, including PubMed, Scopus, and Web of Science, was conducted to identify studies reporting structural, functional, and bioactive properties of NRPS- and PKS-derived compounds. Data extraction focused on compound class, microbial source, biosynthetic pathway, and bioactivity profile. Meta-analytic methods were employed to assess trends in compound discovery and the prevalence of bioactivities across microbial taxa. Results reveal a consistent enrichment of bioactive metabolites in marine and soil-dwelling bacteria, with significant contributions from Bacillus, Streptomyces, and cyanobacterial species. NRPS and PKS systems demonstrated modularity that supports chemical diversity, enabling adaptation to environmental pressures and enhancing ecological fitness. Funnel and forest plot analyses indicate minimal publication bias, confirming the reliability of observed bioactivity trends. These findings underscore the importance of integrating genome mining, metagenomic approaches, and synthetic biology for efficient bioprospecting. The study highlights emerging opportunities to harness microbial biosynthetic machinery for drug discovery and industrial applications, while also emphasizing the need for standardized reporting and functional validation. Overall, microbial biosynthesis represents a sustainable and promising strategy for generating novel bioactive compounds to address pressing therapeutic challenges.