Markers of biosynthetic innovation in the Cyanobacteria

Cyanobacteria, a diverse group of microorganisms, harbor a wealth of specialized metabolites that hold ecological, biomedical and industrial value. However, identifying novel compounds remains challenging due to rediscovery of existing ones and uneven exploration of different taxa. A study analyzed 939 cyanobacterial genomes from 11 orders and five different habitats to pinpoint taxonomic and ecological "hotspots" of biosynthetic potential.

The research identified several biomarkers of biosynthetic innovation, including singleton biosynthetic gene clusters (BGCs) and specialized enzymes, to guide future natural product discovery.

Terpene and ribosomally synthesised and post-translationally modified peptide (RiPP) clusters emerged as the most prevalent BGC types, together accounting for 50% of all identified clusters. These clusters displayed remarkable sequence conservation, averaging 16.41 and 28.10 similarity links per BGC, respectively. In contrast, non-ribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) clusters were less frequent, making up 18.5% and 2.5% of total BGCs, respectively.

These clusters exhibited greater sequence diversity, with a mean of 1.9 and 0.79 similarity links per BGC, respectively.

Enzymes associated with potentially novel chemistries were scarce, with halogenases and cytochrome P450s detected in only 4.9% and 1.27% of BGCs, respectively. Amidine transferases were even rarer, appearing in just 0.42% of BGCs. The study found that symbiotic, terrestrial, and thermal spring cyanobacteria, particularly those belonging to the Nostocales order, exhibited higher biosynthetic potential compared to marine Synechococcales genomes, which showed comparatively lower biosynthetic activity.

Furthermore, putative toxin BGCs were enriched in freshwater Nostocales, Chroococcales, and Oscillatoriales, suggesting a potential link between ecological niche and biosynthetic innovation.