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Int. J. Mol. Sci. 2018, 19(6), 1711; https://doi.org/10.3390/ijms19061711

Blooming of Unusual Cytochrome P450s by Tandem Duplication in the Pathogenic Fungus Conidiobolus coronatus

1
Department of Biochemistry and Microbiology, Faculty of Science and Agriculture, University of Zululand, KwaDlangezwa 3886, South Africa
2
College of Food Science and Technology, Huazhong Agricultural University, Wuhan 430070, China
3
Department of Bacteriology, University of Wisconsin-Madison, 3155 MSB, 1550 Linden Drive, Madison, WI 53706, USA
4
Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN 38163, USA
*
Authors to whom correspondence should be addressed.
Received: 14 March 2018 / Revised: 2 May 2018 / Accepted: 14 May 2018 / Published: 9 June 2018
(This article belongs to the Special Issue Cytochromes P450: Drug Metabolism and Bioactivation)
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Abstract

While the Zygomycete fungus Conidiobolus coronatus primarily infects insects, it can be pathogenic to mammals as well, including humans. High variability in the treatment of this fungal infection with currently available drugs, including azole drugs is a very common phenomenon. Azoles bind to the cytochrome P450 monooxygenases (P450s/CYP) including CYP51, a sterol 14-α-demethylase, inhibiting the synthesis of cell membrane ergosterol and thus leading to the elimination of infecting fungi. Despite P450’s role as a drug target, to date, no information on C. coronatus P450s has been reported. Genome-wide data mining has revealed the presence of 142 P450s grouped into 12 families and 21 subfamilies in C. coronatus. Except for CYP51, the remaining 11 P450 families are new (CYP5854-CYP5864). Despite having a large number of P450s among entomopathogenic fungi, C. coronatus has the lowest number of P450 families, which suggests blooming P450s. Further analysis has revealed that 79% of the same family P450s is tandemly positioned, suggesting that P450 tandem duplication led to the blooming of P450s. The results of this study; i.e., unravelling the C. coronatus P450 content, will certainly help in designing experiments to understand P450s’ role in C. coronatus physiology, including a highly variable response to azole drugs with respect to P450s. View Full-Text
Keywords: cytochrome P450 monooxygenase; Conidiobolus coronatus; drug resistance; entomopathogens; P450 blooms; rare and neglected diseases; rhinoentomophthoramycosis; tandem duplications cytochrome P450 monooxygenase; Conidiobolus coronatus; drug resistance; entomopathogens; P450 blooms; rare and neglected diseases; rhinoentomophthoramycosis; tandem duplications
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Ngwenya, M.L.; Chen, W.; Basson, A.K.; Shandu, J.S.; Yu, J.-H.; Nelson, D.R.; Syed, K. Blooming of Unusual Cytochrome P450s by Tandem Duplication in the Pathogenic Fungus Conidiobolus coronatus. Int. J. Mol. Sci. 2018, 19, 1711.

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