Microbial Bioactives
Microbial Bioactives | Online ISSN 2209-2161
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Volume 6 Number 1 2023
REVIEWS (Open Access)
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) 1-16 https://doi.org/10.25163/microbbioacts.6110669
Submitted: 11 December 2022 Revised: 04 February 2023 Accepted: 14 February 2023 Published: 16 February 2023
Abstract
The oceans, vast and still only partially understood, hold an immense—perhaps underestimated—reservoir of chemical diversity. Within this space, marine microbiomes have emerged as a compelling, if somewhat elusive, source of bioactive secondary metabolites with promising pharmaceutical relevance. Yet, accessing this potential has never been straightforward. Traditional cultivation approaches fall short, largely due to the persistent challenge that most marine microorganisms simply do not grow under standard laboratory conditions. In this context, the present systematic review and meta-analysis attempts to bring together what is currently known, while also, admittedly, revealing what remains uncertain. By integrating findings across genome mining, metagenomics, and experimental optimization studies, this work examines how biosynthetic gene clusters, particularly those encoding nonribosomal peptides and polyketides, are identified, interpreted, and ultimately activated. The results suggest a consistent—though variable—pattern: genome-informed approaches improve discovery efficiency, while strategies such as co-cultivation, elicitation, and metabolic inhibition can significantly enhance metabolite yield, in some cases by several-fold. However, variability across species and methodologies persists, complicating direct comparisons. Taken together, these findings point toward a gradual shift—from exploratory screening to more predictive, systems-driven discovery. While challenges remain, especially in scalability and reproducibility, the integration of genomic insight with ecological and experimental strategies offers a credible pathway toward sustainable natural product development.
Keywords: Marine microbiomes; secondary metabolites; genome mining; metagenomics; biosynthetic gene clusters; natural product discovery; yield enhancement
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