Blooming of unusual cytochrome P450s by tandem duplication in the pathogenic fungus conidiobolus coronatus

Mathula Lancelot Ngwenya, Wanping Chen, Albert Kotze Basson, Jabulani Siyabonga Shandu, Jae Hyuk Yu, David Nelson, Khajamohiddin Syed

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish (US)
Article number1711
JournalInternational journal of molecular sciences
Volume19
Issue number6
DOIs
StatePublished - Jun 9 2018

Fingerprint

Conidiobolus
fungi
cytochromes
azoles
Cytochromes
Fungi
Azoles
drugs
Proteins
Pharmaceutical Preparations
Sterol 14-Demethylase
Mammals
Physiology
Cell membranes
Ergosterol
mammals
data mining
physiology
Data Mining
Data mining

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Blooming of unusual cytochrome P450s by tandem duplication in the pathogenic fungus conidiobolus coronatus. / Ngwenya, Mathula Lancelot; Chen, Wanping; Basson, Albert Kotze; Shandu, Jabulani Siyabonga; Yu, Jae Hyuk; Nelson, David; Syed, Khajamohiddin.

In: International journal of molecular sciences, Vol. 19, No. 6, 1711, 09.06.2018.

Research output: Contribution to journalArticle

Ngwenya, Mathula Lancelot ; Chen, Wanping ; Basson, Albert Kotze ; Shandu, Jabulani Siyabonga ; Yu, Jae Hyuk ; Nelson, David ; Syed, Khajamohiddin. / Blooming of unusual cytochrome P450s by tandem duplication in the pathogenic fungus conidiobolus coronatus. In: International journal of molecular sciences. 2018 ; Vol. 19, No. 6.
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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.",
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