Natural Product Biosynthesis in Myxobacterial Systems

Myxobacteria represent a prolific source of structurally diverse natural products, synthesised by large multifunctional enzyme assemblies such as polyketide synthases and non-ribosomal peptide synthetases. These secondary metabolites serve ecological roles in predation, competition and community signalling, while also offering scaffolds for novel therapeutic agents. Genome sequencing has revealed exceptionally large and dynamic genomes enriched in biosynthetic gene clusters, reflecting both core and accessory pan-genome components that underpin chemical diversity. Comparative metabolomic surveys demonstrate that taxonomic breadth often predicts the discovery of unique metabolite families, encouraging exploration of under-studied genera. Marine and terrestrial myxobacteria both contribute distinct biosynthetic repertoires, with habitat-specific gene clusters encoding polyketides, peptides, hybrids and terpenoids. Mechanistic studies of tailoring enzymes, self-resistance factors and regulatory circuits have begun to unveil principles governing chain assembly, modification and product export. Integration of phylogenetic, genomic and chemical data continues to refine strategies for genome mining, heterologous expression and engineering of myxobacterial pathways, underpinning their global importance for drug discovery and synthetic biology.

Research from Nature Portfolio

Large-scale metabolite profiling across several thousand myxobacterial strains has established a clear correlation between phylogenetic distance and secondary metabolite novelty. This work systematically compared production profiles by mass spectrometry, revealing that the likelihood of unearthing new chemical scaffolds increases when sampling across genera rather than within the same genus. The study also identified novel phosphorylated polyketide structures, illustrating how untargeted surveys can lead to unexpected scaffolds. In a complementary effort, comparative genomic and metabolomic analysis of marine myxobacteria strains uncovered exceptionally large genomes with a small conserved core and numerous unique coding sequences. Polyketide and terpene gene clusters dominated the predicted specialised metabolite repertoire, while non-ribosomal peptide and hybrid clusters were largely strain-specific. Metabolomic data confirmed a high degree of chemical divergence between strains, highlighting marine myxobacteria as fertile ground for novel natural products.

Natural Product Biosynthesis in Myxobacterial Systems publication trend

The graph below shows the total number of articles in natural product biosynthesis in myxobacterial systems 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 proteins responsible for the assembly of a particular secondary metabolite.

Non-ribosomal peptide synthetase (NRPS): A large multi-domain enzyme complex that assembles peptides independently of the ribosome, often incorporating non-proteinogenic amino acids.

Polyketide synthase (PKS): A modular megasynthase that catalyses the stepwise condensation of acyl-CoA building blocks to form polyketide chains.

Pan-genome: The full complement of genes within a species or genus, comprising both the core genome shared by all strains and the accessory genome unique to subsets of strains.

Secondary metabolite: A low-molecular-weight compound not directly involved in primary metabolism but often conferring ecological advantages such as defence or signalling.

References

1. Deciphering the Biosynthesis and Physiological Function of 5‑Methylated Pyrazinones Produced by Myxobacteria. ACS Central Science (2024).
2. Correlating chemical diversity with taxonomic distance for discovery of natural products in myxobacteria. Nature Communications (2018).
3. Analysis of the Genome and Metabolome of Marine Myxobacteria Reveals High Potential for Biosynthesis of Novel Specialized Metabolites. Scientific Reports (2018).
4. Genome Sequencing and Pan-Genome Analysis of 23 Corallococcus spp. Strains Reveal Unexpected Diversity, With Particular Plasticity of Predatory Gene Sets. Frontiers in Microbiology (2018).
5. Myxobacteria Are Able to Prey Broadly upon Clinically-Relevant Pathogens, Exhibiting a Prey Range Which Cannot Be Explained by Phylogeny. Frontiers in Microbiology (2017).