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

**Fanele Cabangile Mnguni 1, Tiara Padayachee 1, Wanping Chen 2, Dominik Gront 3, Jae-Hyuk Yu 4,5, David R. Nelson 6,\* and Khajamohiddin Syed 1,\***


Received: 18 January 2020; Accepted: 13 February 2020; Published: 7 July 2020

**Abstract:** Unraveling the role of cytochrome P450 monooxygenases (CYPs/P450s), heme-thiolate proteins present in living and non-living entities, in secondary metabolite synthesis is gaining momentum. In this direction, in this study, we analyzed the genomes of 203 *Streptomyces* species for P450s and unraveled their association with secondary metabolism. Our analyses revealed the presence of 5460 P450s, grouped into 253 families and 698 subfamilies. The CYP107 family was found to be conserved and highly populated in *Streptomyces* and *Bacillus* species, indicating its key role in the synthesis of secondary metabolites. *Streptomyces* species had a higher number of P450s than *Bacillus* and cyanobacterial species. The average number of secondary metabolite biosynthetic gene clusters (BGCs) and the number of P450s located in BGCs were higher in *Streptomyces* species than in *Bacillus*, mycobacterial, and cyanobacterial species, corroborating the superior capacity of *Streptomyces* species for generating diverse secondary metabolites. Functional analysis *via* data mining confirmed that many *Streptomyces* P450s 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) of *Streptomyces* species, revealing the P450s' association with secondary metabolite synthesis in *Streptomyces* species. Future studies should include the selection of *Streptomyces* species with a higher number of P450s and BGCs and explore the biotechnological value of secondary metabolites they produce.

**Keywords:** *Streptomyces*; *Mycobacterium*; *Bacillus*; *Cyanobacteria*; cytochrome P450 monooxygenases; secondary metabolites; biosynthetic gene clusters; terpenes; polyketides; P450 blooming; non-ribosomal peptides
