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. 2021 May 24;22(11):5542.
doi: 10.3390/ijms22115542.

Ancient Bacterial Class Alphaproteobacteria Cytochrome P450 Monooxygenases Can Be Found in Other Bacterial Species

Nomfundo Nzuza  1 , Tiara Padayachee  1 , Puleng Rosinah Syed  2 , Justyna Dorota Kryś  3 , Wanping Chen  4 , Dominik Gront  3 , David R Nelson  5 , Khajamohiddin Syed  1
Affiliations

Ancient Bacterial Class Alphaproteobacteria Cytochrome P450 Monooxygenases Can Be Found in Other Bacterial Species

Nomfundo Nzuza et al. Int J Mol Sci. .

Abstract

Cytochrome P450 monooxygenases (CYPs/P450s), heme-thiolate proteins, are well-known players in the generation of chemicals valuable to humans and as a drug target against pathogens. Understanding the evolution of P450s in a bacterial population is gaining momentum. In this study, we report comprehensive analysis of P450s in the ancient group of the bacterial class Alphaproteobacteria. Genome data mining and annotation of P450s in 599 alphaproteobacterial species belonging to 164 genera revealed the presence of P450s in only 241 species belonging to 82 genera that are grouped into 143 P450 families and 214 P450 subfamilies, including 77 new P450 families. Alphaproteobacterial species have the highest average number of P450s compared to Firmicutes species and cyanobacterial species. The lowest percentage of alphaproteobacterial species P450s (2.4%) was found to be part of secondary metabolite biosynthetic gene clusters (BGCs), compared other bacterial species, indicating that during evolution large numbers of P450s became part of BGCs in other bacterial species. Our study identified that some of the P450 families found in alphaproteobacterial species were passed to other bacterial species. This is the first study to report on the identification of CYP125 P450, cholesterol and cholest-4-en-3-one hydroxylase in alphaproteobacterial species (Phenylobacterium zucineum) and to predict cholesterol side-chain oxidation capability (based on homolog proteins) by P. zucineum.

Keywords: Alphaproteobacteria; CYP125; annotation; biosynthetic gene clusters; cholesterol oxidation; cytochrome P450 monooxygenase; genome data mining.

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Conflict of interest statement

The authors declare no conflict of interest and the funders had no role in the design of the study; 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
Comparative analysis of P450 statistics in the bacterial class Alphaproteobacteria. Detailed information is presented in Table S1.
Figure 2
Figure 2
Phylogenetic analysis of alphaproteobacterial P450s. P450 families that are expanded in these species were highlighted in different colors and indicated in the figure. Alphaproteobacterial P450 protein sequences used to construct the phylogenetic tree are presented in Supplementary Dataset 1.
Figure 3
Figure 3
Heat map figure representing the presence or absence of cytochrome P450 families in 599 alphaproteobacterial species. The data have been represented as −3 for family absence (green) and 3 for family presence (red). One hundred and forty-three alphaproteobacterial species form the vertical axis and 214 P450 families form the horizontal axis. The respective data used in the generation of this figure are presented in Supplementary Dataset 2.
Figure 4
Figure 4
Comparative analysis of types of secondary metabolite BGCs in alphaproteobacterial species. BGCs that are populated in alphaproteobacterial species were presented in the figure. The number at the top of each bar represents the total number of clusters. Detailed information is presented in Supplementary Dataset 3.
Figure 5
Figure 5
Comparative analysis of P450 families among different bacterial species. The number of P450 families indicated with a number (bold case) and P450 families that are common between alphaproteobacterial species and other bacterial species were listed in the figure.
See this image and copyright information in PMC

References

    1. Yamazaki H. Fifty Years of Cytochrome P450 Research. Springer Japan; Tokyo, Japan: 2014. pp. 1–409.
    1. Li Z., Jiang Y., Guengerich F.P., Ma L., Li S., Zhang W. Engineering cytochrome P450 enzyme systems for biomedical and biotechnological applications. J. Biol. Chem. 2020;295:833–849. doi: 10.1016/S0021-9258(17)49939-X. - DOI - PMC - PubMed
    1. Urlacher V.B., Girhard M. Cytochrome P450 monooxygenases in biotechnology and synthetic biology. Trends Biotechnol. 2019;37:882–897. doi: 10.1016/j.tibtech.2019.01.001. - DOI - PubMed
    1. Nelson D.R. Cytochrome P450 diversity in the tree of life. Biochim. Biophys. Acta (BBA) Proteins Proteom. 2018;1866:141–154. doi: 10.1016/j.bbapap.2017.05.003. - DOI - PMC - PubMed
    1. Lamb D.C., Follmer A.H., Goldstone J.V., Nelson D.R., Warrilow A.G., Price C.L., True M.Y., Kelly S.L., Poulos T.L., Stegeman J.J. On the occurrence of cytochrome P450 in viruses. Proc. Natl. Acad. Sci. USA. 2019;116:12343–12352. doi: 10.1073/pnas.1901080116. - DOI - PMC - PubMed

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