Complex secondary metabolite potential of the group V cyanobacteria revealed through whole genome sequencing

Cyanobacteria are known to produce a large number of bioactive natural products, known as secondary metabolites, many of which have potential pharmaceutical interest. There are currently five groups of cyanobacteria that are classified based on their morphology; of these, the group V cyanobacteria are considered to be the most advanced. Recent genome sequencing projects have led to an increase in the number of publically available group V cyanobacterial genomes, however, the secondary metabolite potential of the majority of these organisms remains elusive. In order to investigate this lapse in knowledge, we sequenced the genomes of two group V cyanobacteria, Hapalosiphon welwitschii UH strain IC-52-3 and Westiella intricata UH strain HT-29-1, and performed genome mining of all 11 publically available group V cyanobacterial genomes. In total, 18 complete orphan NRPS/PKS gene clusters were identified from the group V cyanobacteria. Additionally, hapalosin, a cyclic depsipeptide known to reverse P-glycoprotein multiple drug resistance, has previously only been identified within the cyanobacterium  H. welwitschii UH strain IC-52-3. However, the hapalosin biosynthetic gene cluster was identified within three group V cyanobacterial genomes. A number of ribosomally synthesised gene clusters (including cyanobactin, microviridin and bacteriocin gene clusters) were also identified. Furthermore, gene clusters encoding the biosynthesis of mycosporine-like amino acids, scytonemin, hydrocarbons, terpenes and the hapalindole and welwitindolinone alkaloids were also identified. Genome mining has revealed the diversity, abundance and complex nature of secondary metabolite potential of this advanced group of cyanobacteria.