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Comprehensive Analyses of Cytochrome P450 Monooxygenases and Secondary Metabolite Biosynthetic Gene Clusters in Cyanobacteria

1
Department of Biochemistry and Microbiology, Faculty of Science and Agriculture, University of Zululand, KwaDlangezwa 3886, South Africa
2
Department of Molecular Microbiology and Genetics, University of Göttingen, 37077 Göttingen, Germany
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Department of Bacteriology, University of Wisconsin-Madison, 3155 MSB, 1550 Linden Drive, Madison, WI 53706, USA
4
Department of Systems Biotechnology, Konkuk University, Seoul 05029, Korea
5
Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN 38163, USA
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(2), 656; https://doi.org/10.3390/ijms21020656
Received: 22 December 2019 / Revised: 13 January 2020 / Accepted: 15 January 2020 / Published: 19 January 2020
(This article belongs to the Special Issue Cytochromes P450: Drug Metabolism, Bioactivation and Biodiversity 2.0)
The prokaryotic phylum Cyanobacteria are some of the oldest known photosynthetic organisms responsible for the oxygenation of the earth. Cyanobacterial species have been recognised as a prosperous source of bioactive secondary metabolites with antibacterial, antiviral, antifungal and/or anticancer activities. Cytochrome P450 monooxygenases (CYPs/P450s) contribute to the production and diversity of various secondary metabolites. To better understand the metabolic potential of cyanobacterial species, we have carried out comprehensive analyses of P450s, predicted secondary metabolite biosynthetic gene clusters (BGCs), and P450s located in secondary metabolite BGCs. Analysis of the genomes of 114 cyanobacterial species identified 341 P450s in 88 species, belonging to 36 families and 79 subfamilies. In total, 770 secondary metabolite BGCs were found in 103 cyanobacterial species. Only 8% of P450s were found to be part of BGCs. Comparative analyses with other bacteria Bacillus, Streptomyces and mycobacterial species have revealed a lower number of P450s and BGCs and a percentage of P450s forming part of BGCs in cyanobacterial species. A mathematical formula presented in this study revealed that cyanobacterial species have the highest gene-cluster diversity percentage compared to Bacillus and mycobacterial species, indicating that these diverse gene clusters are destined to produce different types of secondary metabolites. The study provides fundamental knowledge of P450s and those associated with secondary metabolism in cyanobacterial species, which may illuminate their value for the pharmaceutical and cosmetics industries. View Full-Text
Keywords: cytochromes P450 monooxygenases; secondary metabolites; Cyanobacteria; biosynthetic gene clusters; gene-cluster diversity percentage; mathematical formula; phylogenetic analysis cytochromes P450 monooxygenases; secondary metabolites; Cyanobacteria; biosynthetic gene clusters; gene-cluster diversity percentage; mathematical formula; phylogenetic analysis
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Khumalo, M.J.; Nzuza, N.; Padayachee, T.; Chen, W.; Yu, J.-H.; Nelson, D.R.; Syed, K. Comprehensive Analyses of Cytochrome P450 Monooxygenases and Secondary Metabolite Biosynthetic Gene Clusters in Cyanobacteria. Int. J. Mol. Sci. 2020, 21, 656.

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