Distribution and Diversity of Cytochrome P450 Monooxygenases in the Fungal Class Tremellomycetes.

Olufunmilayo Olukemi Akapo,David R Nelson,Tiara Padayachee,Wanping Chen,Jae-Hyuk Yu,Abidemi Paul Kappo,Khajamohiddin Syed

doi:10.3390/ijms20122889

Abstract

Tremellomycetes, a fungal class in the subphylum Agaricomycotina, contain well-known opportunistic and emerging human pathogens. The azole drug fluconazole, used in the treatment of diseases caused by some species of Tremellomycetes, inhibits cytochrome P450 monooxygenase CYP51, an enzyme that converts lanosterol into an essential component of the fungal cell membrane ergosterol. Studies indicate that mutations and over-expression of CYP51 in species of Tremellomycetes are one of the reasons for fluconazole resistance. Moreover, the novel drug, VT-1129, that is in the pipeline is reported to exert its effect by binding and inhibiting CYP51. Despite the importance of CYPs, the CYP repertoire in species of Tremellomycetes has not been reported to date. This study intends to address this research gap. Comprehensive genome-wide CYP analysis revealed the presence of 203 CYPs (excluding 16 pseudo-CYPs) in 23 species of Tremellomycetes that can be grouped into 38 CYP families and 72 CYP subfamilies. Twenty-three CYP families are new and three CYP families (CYP5139, CYP51 and CYP61) were conserved across 23 species of Tremellomycetes. Pathogenic cryptococcal species have 50% fewer CYP genes than non-pathogenic species. The results of this study will serve as reference for future annotation and characterization of CYPs in species of Tremellomycetes.

Highlights

Cryptococcosis is a fungal infectious disease ubiquitously distributed around the world [1]
C. curvatus and C. terricola have the highest number of CYPs (16 CYPs each), and C. gattii VGIV IND107 has the lowest number of CYPs (Figure 1)
Almost 50% fewer CYPs were found in pathogenic cryptococcal species compared to non-pathogenic cryptococcal species (Figure 1)

Summary

Introduction

Cryptococcosis is a fungal infectious disease ubiquitously distributed around the world [1]. Cryptococcus neoformans and C. gattii, are the main infectious agents causing cryptococcal meningitis in both immunocompetent and immunocompromised humans [1,2,3,4] This disease is the major cause of morbidity and mortality among people living with advanced HIV and annually accounts for 15% of all HIV-related deaths globally [5,6]. The burden of HIV-associated cryptococcal disease in Sub-Saharan Africa is alarming, as 73% of deaths in the world are reported in this region [5,6]. Apart from these opportunistic pathogens, the genus Cryptococcus contains species with biotechnological potential (Table 1). C. amylolentus is closely related to the pathogenic C. neoformans and is extensively used for comparative studies to identify the pathogenic traits in C. neoformans [7]

Methods

Results

Conclusion