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

Fanele Cabangile Mnguni,Dominik Gront,Jae-Hyuk Yu,David R Nelson,Tiara Padayachee,Wanping Chen,Khajamohiddin Syed

doi:10.3390/ijms21134814

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.

Highlights

Cytochrome P450 monooxygenases (CYPs/P450s) are biotechnologically valuable enzymes [1].P450s have heme, an iron(III)-containing porphyrin, as a prosthetic group in their structure [2]
Comparative analysis of key P450 features among different bacterial species revealed that Streptomyces species had a greater number of P450s, more secondary metabolite biosynthetic gene cluster. Symbol (BGC), and the highest number of P450s as part of BGCs compared to the bacterial species belonging to the genera Bacillus, Mycobacterium, and Cyanobacteria
This was true for Streptomyces species, as large number of P450s were found to be involved in the generation of diverse secondary metabolites

Summary

Introduction

Cytochrome P450 monooxygenases (CYPs/P450s) are biotechnologically valuable enzymes [1].P450s have heme (protoporphyrin IX), an iron(III)-containing porphyrin, as a prosthetic group in their structure [2]. Because of the presence of this prosthetic group, these enzymes absorb wavelengths at 450 nm; the name P450s has been assigned to these proteins [3,4,5,6]. The regio- and stereo-specific catalytic nature of these enzymes makes them essential for the survival of some organisms, and these enzymes are good drug targets in the case of pathogenic organisms [9,10,11,12,13] Application of these enzymes in all fields of research continues, and excellent success has been achieved in using them for the production of substances valuable to humans or as drug targets or in drug metabolism, as reported previously [1]. One of the applications of P450s currently being explored is their role in the production of secondary metabolites, compounds with potential biotechnological value, owing to their stereo- and regio-specific enzymatic activity, which contributes to the diversity of secondary metabolites [14,15,16]

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Conclusion