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. 2022 Apr 21;10(5):871.
doi: 10.3390/microorganisms10050871.

An Unprecedented Number of Cytochrome P450s Are Involved in Secondary Metabolism in Salinispora Species

Nsikelelo Allison Malinga  1 , Nomfundo Nzuza  1 , Tiara Padayachee  1 , Puleng Rosinah Syed  2 , Rajshekhar Karpoormath  2 , Dominik Gront  3 , David R Nelson  4 , Khajamohiddin Syed  1
Affiliations

An Unprecedented Number of Cytochrome P450s Are Involved in Secondary Metabolism in Salinispora Species

Nsikelelo Allison Malinga et al. Microorganisms. .

Abstract

Cytochrome P450 monooxygenases (CYPs/P450s) are heme thiolate proteins present in species across the biological kingdoms. By virtue of their broad substrate promiscuity and regio- and stereo-selectivity, these enzymes enhance or attribute diversity to secondary metabolites. Actinomycetes species are well-known producers of secondary metabolites, especially Salinispora species. Despite the importance of P450s, a comprehensive comparative analysis of P450s and their role in secondary metabolism in Salinispora species is not reported. We therefore analyzed P450s in 126 strains from three different species Salinispora arenicola, S. pacifica, and S. tropica. The study revealed the presence of 2643 P450s that can be grouped into 45 families and 103 subfamilies. CYP107 and CYP125 families are conserved, and CYP105 and CYP107 families are bloomed (a P450 family with many members) across Salinispora species. Analysis of P450s that are part of secondary metabolite biosynthetic gene clusters (smBGCs) revealed Salinispora species have an unprecedented number of P450s (1236 P450s-47%) part of smBGCs compared to other bacterial species belonging to the genera Streptomyces (23%) and Mycobacterium (11%), phyla Cyanobacteria (8%) and Firmicutes (18%) and the classes Alphaproteobacteria (2%) and Gammaproteobacteria (18%). A peculiar characteristic of up to six P450s in smBGCs was observed in Salinispora species. Future characterization Salinispora species P450s and their smBGCs have the potential for discovering novel secondary metabolites.

Keywords: Mycobacterium; Salinispora arenicola; Streptomyces; actinomycete; biosynthetic gene clusters; cytochrome P450; diversity; genome-data mining; marine; natural products; secondary metabolites.

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Conflict of interest statement

The authors declare no conflict of interest, and the funders had no role in the study’s design, in the collection, analyses, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Phylogenetic analysis of Salinispora species P450s. 2643 P450s were used to construct the tree, and the members of the eight most abundant P450 families are highlighted in different colors and indicated in the figure. P450 protein sequences used to build the tree are listed in Table S2. A high-resolution phylogenetic tree is provided in Figure S1.
Figure 2
Figure 2
Heat-map of P450 family conservation or co-presence analysis in Salinispora species. In the heat-map, the presence and absence of P450 families are indicated in red and green colors. The horizontal axis represents P450 families, and the vertical axis represents Salinispora species.
Figure 3
Figure 3
Comparative analysis of P450s associated with secondary metabolism in Salinispora species. The P450 family name, number of P450s, and the percentage of the total number of P450s that are part of secondary metabolite biosynthetic gene clusters (smBGCs) are presented in the figure. Detailed information on secondary metabolite clusters, species, and P450s are shown in Table S1.
See this image and copyright information in PMC

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