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

Makhosazana Jabulile Khumalo,Tiara Padayachee,Khajamohiddin Syed,David R Nelson,Wanping Chen,Nomfundo Nzuza,Jae-Hyuk Yu

doi:10.3390/ijms21020656

Abstract

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.

Highlights

Cyanobacteria are thought to be some of the oldest known photosynthetic organisms that played a major role in the evolution of life by contributing to the oxygenation of the earth’s atmosphere [1,2,3,4,5]
The analysis revealed the presence of 13 P450-fragments and 15 P450 false positives in different cyanobacterial species (Table S2)
This study is an attempt to provide a complete picture of P450 enzymes in different cyanobacterial species as these enzymes are the key players in primary and secondary metabolism of organisms, including the production of different secondary metabolites

Summary

Introduction

Cyanobacteria are thought to be some of the oldest known photosynthetic organisms that played a major role in the evolution of life by contributing to the oxygenation of the earth’s atmosphere [1,2,3,4,5]. To survive in a wide range of environments, cyanobacterial species produce diverse natural products comprising both primary and secondary metabolites belonging to the group’s non-ribosomal proteins, polyketides, and terpenes and alkaloids. These products have varying activities of anticancer, antiviral, and ultraviolet-protective activities, as well as hepatotoxicity and neurotoxicity [10,11]. Many cyanobacterial species are used as model organisms to understand fundamental processes such as photosynthesis, nitrogen fixation, and circadian rhythm [12,13,14] Owing to their amenability to gene manipulation, these organisms have been genetically modified/engineered for the production of valuable human compounds [15,16].

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Conclusion