More P450s Are Involved in Secondary Metabolite Biosynthesis in Streptomyces Compared to Bacillus, Cyanobacteria, and Mycobacterium

Unraveling the role of cytochrome P450 monooxygenases (CYPs/P450s), heme-thiolateproteins present in living and non-living entities, in secondary metabolite synthesis is gainingmomentum. In this direction, in this study, we analyzed the genomes of 203Streptomycesspeciesfor P450s and unraveled their association with secondary metabolism. Our analyses revealed thepresence of 5460 P450s, grouped into 253 families and 698 subfamilies. The CYP107 family wasfound to be conserved and highly populated inStreptomycesandBacillusspecies, indicating its keyrole in the synthesis of secondary metabolites.Streptomycesspecies had a higher number of P450sthanBacillusand cyanobacterial species. The average number of secondary metabolite biosyntheticgene clusters (BGCs) and the number of P450s located in BGCs were higher inStreptomycesspeciesthan inBacillus, mycobacterial, and cyanobacterial species, corroborating the superior capacity ofStreptomycesspecies for generating diverse secondary metabolites. Functional analysisviadata miningconfirmed that manyStreptomycesP450s are involved in the biosynthesis of secondary metabolites.This study was the first of its kind to conduct a comparative analysis of P450s in such a large number(203) ofStreptomycesspecies, revealing the P450s’ association with secondary metabolite synthesisinStreptomycesspecies. Future studies should include the selection ofStreptomycesspecies with ahigher number of P450s and BGCs and explore the biotechnological value of secondary metabolitesthey produce.