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

**Olufunmilayo Olukemi Akapo 1, Tiara Padayachee 1, Wanping Chen 2, Abidemi Paul Kappo 1, Jae-Hyuk Yu 3,4, David R. Nelson 5,\* and Khajamohiddin Syed 1,\***


Received: 20 April 2019; Accepted: 30 May 2019; Published: 13 June 2019

**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*.

**Keywords:** *cryptococcus*; *cryptococcus neoformans*; cytochrome P450 monooxygenase; CYP51; fungal pathogens; genome data-mining; human pathogens; CYP diversity analysis; *tremellomycetes*; *trichosporon*
