Molecular evolutionary dynamics of cytochrome P450 monooxygenases across kingdoms: Special focus on mycobacterial P450s.
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.
Unit for Drug Discovery Research, Department of Health Sciences, Faculty of Health and Environmental Sciences, Central University of Technology, Bloemfontein 9300, Free State, South Africa.
Mohammad
M
Parvez
Unit for Drug Discovery Research, Department of Health Sciences, Faculty of Health and Environmental Sciences, Central University of Technology, Bloemfontein 9300, Free State, South Africa.
Lehlohonolo Benedict
LB
Qhanya
Unit for Drug Discovery Research, Department of Health Sciences, Faculty of Health and Environmental Sciences, Central University of Technology, Bloemfontein 9300, Free State, South Africa.
Ntsane Trevor
NT
Mthakathi
Unit for Drug Discovery Research, Department of Health Sciences, Faculty of Health and Environmental Sciences, Central University of Technology, Bloemfontein 9300, Free State, South Africa.
Ipeleng Kopano Rosinah
IK
Kgosiemang
Unit for Drug Discovery Research, Department of Health Sciences, Faculty of Health and Environmental Sciences, Central University of Technology, Bloemfontein 9300, Free State, South Africa.
Hans Denis
HD
Bamal
Department of Medical Microbiology and Immunology, 6-020 Katz Group Centre, University of Alberta, Edmonton, Alberta T6G 2E1, Canada.
Nataraj Sekhar
NS
Pagadala
College of Informatics, Huazhong Agricultural University, Wuhan, Hubei Province, China.
Ting
T
Xie
College of Food Science and Technology, Huazhong Agricultural University, Wuhan, Hubei Province, China.
Haoran
H
Yang
College of Food Science and Technology, Huazhong Agricultural University, Wuhan, Hubei Province, China.
Hengye
H
Chen
Faculty of Natural and Agricultural Science, Department of Microbial, Biochemical and Food Biotechnology, University of the Free State, P.O. Box 339, Bloemfontein, 9300, South Africa.
Chrispian William
CW
Theron
Unit for Drug Discovery Research, Department of Health Sciences, Faculty of Health and Environmental Sciences, Central University of Technology, Bloemfontein 9300, Free State, South Africa.
Richie
R
Monyaki
Unit for Drug Discovery Research, Department of Health Sciences, Faculty of Health and Environmental Sciences, Central University of Technology, Bloemfontein 9300, Free State, South Africa.
Seiso Caiphus
SC
Raselemane
Unit for Drug Discovery Research, Department of Health Sciences, Faculty of Health and Environmental Sciences, Central University of Technology, Bloemfontein 9300, Free State, South Africa.
Vuyani
V
Salewe
Unit for Drug Discovery Research, Department of Health Sciences, Faculty of Health and Environmental Sciences, Central University of Technology, Bloemfontein 9300, Free State, South Africa.
Bogadi Lorato
BL
Mongale
Unit for Drug Discovery Research, Department of Health Sciences, Faculty of Health and Environmental Sciences, Central University of Technology, Bloemfontein 9300, Free State, South Africa.
Retshedisitswe Godfrey
RG
Matowane
Unit for Drug Discovery Research, Department of Health Sciences, Faculty of Health and Environmental Sciences, Central University of Technology, Bloemfontein 9300, Free State, South Africa.
Sara Mohamed Hasaan
SM
Abdalla
Unit for Drug Discovery Research, Department of Health Sciences, Faculty of Health and Environmental Sciences, Central University of Technology, Bloemfontein 9300, Free State, South Africa.
Wool Isaac
WI
Booi
Unit for Drug Discovery Research, Department of Health Sciences, Faculty of Health and Environmental Sciences, Central University of Technology, Bloemfontein 9300, Free State, South Africa.
Mari
M
van Wyk
Unit for Drug Discovery Research, Department of Health Sciences, Faculty of Health and Environmental Sciences, Central University of Technology, Bloemfontein 9300, Free State, South Africa.
Dedré
D
Olivier
Faculty of Natural and Agricultural Science, Department of Microbial, Biochemical and Food Biotechnology, University of the Free State, P.O. Box 339, Bloemfontein, 9300, South Africa.
Charlotte E
CE
Boucher
Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
David R
DR
Nelson
Department of Physics, University of Alberta, Edmonton, Alberta T6G 2J1, Canada.
Jack A
JA
Tuszynski
Institute of Infectious Disease &Molecular Medicine; Department of Integrative Biomedical Sciences, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa.
Jonathan Michael
JM
Blackburn
Department of Bacteriology, University of Wisconsin-Madison, 3155 MSB, 1550 Linden Drive, Madison WI 53706, USA.
Jae-Hyuk
JH
Yu
Unit for Drug Discovery Research, Department of Health Sciences, Faculty of Health and Environmental Sciences, Central University of Technology, Bloemfontein 9300, Free State, South Africa.
Samson Sitheni
SS
Mashele
College of Food Science and Technology, Huazhong Agricultural University, Wuhan, Hubei Province, China.
Wanping
W
Chen
Unit for Drug Discovery Research, Department of Health Sciences, Faculty of Health and Environmental Sciences, Central University of Technology, Bloemfontein 9300, Free State, South Africa.
Khajamohiddin
K
Syed
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D019143:Evolution, Molecular; D016680:Genome, Bacterial; D016681:Genome, Fungal; D018745:Genome, Plant; D056004:Molecular Dynamics Simulation; D009161:Mycobacterium / Q000235:genetics*; D010802:Phylogeny
D003577:Cytochrome P-450 Enzyme System