Biosynthesis of Bioactive Natural Products from Marine Organisms

The marine environment is a prolific source of structurally diverse natural products with significant bioactivities, including antibiotic, antifungal, anticancer and anti-inflammatory properties. Biosynthesis in marine organisms is mediated by specialised enzyme systems—most notably polyketide synthases and nonribosomal peptide synthetases—encoded within biosynthetic gene clusters (BGCs). These pathways often involve iterative or modular assembly lines that incorporate unusual substrates, tailoring enzymes and post-assembly modifications to yield complex chemical scaffolds. Advances in genomics, metabolomics and synthetic biology have enabled the discovery and engineering of new compounds by linking gene clusters to their products, facilitating heterologous expression and pathway refactoring. Ecologically, these metabolites serve roles in defence, competition and symbiosis, and they offer templates for drug discovery and sustainable production through microbial fermentation or engineered hosts.

Research from Nature Portfolio

Global comparative analysis of BGCs across entomopathogenic symbionts has revealed a remarkably conserved core of biosynthetic families alongside unique pathways tailored to specific ecological niches. Pangenome-wide surveys identified over a thousand BGCs grouped into distinct classes, including nonribosomal peptide, polyketide and hybrid clusters. Functional characterisation of selected clusters uncovered novel eukaryotic proteasome inhibitors, insect virulence factors, metallophores and immunosuppressants. This work demonstrates how integrative genomics and targeted expression can decode the chemical lexicon of symbiotic bacteria, elucidating the roles of microbial metabolites in tripartite interactions and guiding the prioritisation of clusters for biotechnological exploitation.

Biosynthesis of Bioactive Natural Products from Marine Organisms publication trend

The graph below shows the total number of articles in biosynthesis of bioactive natural products from marine organisms across all publications each year (not limited to Nature Index journals).

Technical terms

Biosynthetic gene cluster (BGC): A contiguous set of genes encoding enzymes and regulatory elements responsible for the synthesis of a particular natural product.

Polyketide synthase (PKS): A multi-domain enzyme complex that assembles polyketides through successive condensation of acyl-CoA precursors.

Nonribosomal peptide synthetase (NRPS): A modular enzyme that catalyses the assembly of peptide natural products independent of the ribosome.

Genome mining: The use of computational tools to identify and characterise biosynthetic potential within genomic sequences.

References

1. Isocyanides inhibit bacterial pathogens by covalent targeting of essential metabolic enzymes. Chemical Science (2024).
2. Genus Acanthella—A Wealthy Treasure: Secondary Metabolites, Synthesis, Biosynthesis, and Bioactivities. Marine Drugs (2023).
3. Global analysis of biosynthetic gene clusters reveals conserved and unique natural products in entomopathogenic nematode-symbiotic bacteria. Nature Chemistry (2022).