Molecular evolutionary dynamics of cytochrome P450 monooxygenases across kingdoms: Special focus on mycobacterial P450s
Autor: | Lehlohonolo Benedict Qhanya, Khajamohiddin Syed, Jae-Hyuk Yu, Richie Monyaki, Jack A. Tuszynski, Retshedisitswe Godfrey Matowane, Hans Denis Bamal, Mohammad Parvez, Wool Isaac Booi, Vuyani Salewe, Sara Mohamed Hasaan Abdalla, Haoran Yang, Ting Xie, Ntsane Trevor Mthakathi, Jonathan M. Blackburn, Hengye Chen, David R. Nelson, Samson Sitheni Mashele, Chrispian W. Theron, Ipeleng Kopano Rosinah Kgosiemang, Charlotte E. Boucher, Dedré Olivier, Seiso Caiphus Raselemane, Mari van Wyk, Bogadi Lorato Mongale, Nataraj Sekhar Pagadala, Wanping Chen |
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Jazyk: | angličtina |
Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Molecular Dynamics Simulation digestive system Genome Article Mycobacterium Evolution Molecular 03 medical and health sciences Cytochrome P-450 Enzyme System Phylogenetics Molecular evolution polycyclic compounds Animals Evolutionary dynamics Phylogeny Genetics Multidisciplinary 030102 biochemistry & molecular biology Phylogenetic tree biology Cytochrome P450 Monooxygenase 030104 developmental biology biology.protein Genome Fungal Genome Bacterial Genome Plant Function (biology) |
Zdroj: | Scientific Reports |
ISSN: | 2045-2322 |
DOI: | 10.1038/srep33099 |
Popis: | Since the initial identification of cytochrome P450 monooxygenases (CYPs/P450s), great progress has been made in understanding their structure-function relationship, diversity and application in producing compounds beneficial to humans. However, the molecular evolution of P450s in terms of their dynamics both at protein and DNA levels and functional conservation across kingdoms still needs investigation. In this study, we analyzed 17 598 P450s belonging to 113 P450 families (bacteria −42; fungi −19; plant −28; animal −22; plant and animal −1 and common P450 family −1) and found highly conserved and rapidly evolving P450 families. Results suggested that bacterial P450s, particularly P450s belonging to mycobacteria, are highly conserved both at protein and DNA levels. Mycobacteria possess the highest P450 diversity percentage compared to other microbes and have a high coverage of P450s (≥1%) in their genomes, as found in fungi and plants. Phylogenetic and functional analyses revealed the functional conservation of P450s despite belonging to different biological kingdoms, suggesting the adherence of P450s to their innate function such as their involvement in either generation or oxidation of steroids and structurally related molecules, fatty acids and terpenoids. This study’s results offer new understanding of the dynamic structural nature of P450s. |
Databáze: | OpenAIRE |
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