The Cytochrome P450 Complement (CYPome) of Leishmania Leads to the Discovery of a Plant Like Cytochrome P450 Sub-Family CYP710C1 Gene

Abstract

Cytochrome P450 (CYP) is a super-family of heme-containing monooxygenases and is involved in the metabolism of endogenous xenobiotic compounds. A genome-wide analysis of the complete cytochrome P450 complement (CYPome) in Leishmania species is presented here. Genome database search algorithms of 20 strains of Leishmania species and 3 strains of Trypanosoma brucei was employed to describe the complete CYPome. Motif search analysis and phylogenetic studies were carried out to investigate the sequence diversity and distribution of different CYPs in Leishmania in comparison to fungi, humans, plants and prokaryotes. In silico analysis predicted the presence of genes belonging to CYP51 and a plantlike CYP710C gene that encodes a plant-like sterol C-22 desaturase, a key enzyme in stigmasterol biosynthesis. This is the first report for the comparative analysis of stigma sterol biosynthetic pathway genes in Leishmania donovani, Arabidopsis thaliana and Candida albicans. We provide experimental evidence of stigmasterol presence in L. donovani promastigotes. We further demonstrate that amphotericin B-resistant L. donovani accumulated stigmasterol as the major sterol and ergosterol to a lesser extent. In conclusion, this study is presumably the first comprehensive report on CYPome of Leishmania and molecular evidence of a plant-like sterol C-22 desaturase gene in Leishmania.