The Cytochrome P450 Complement (CYPome) of Leishmania leads to the discovery of a plant like Cytochrome P450 subfamily CYP710C1 gene

Abstract

Cytochrome P450 (CYP) is a superfamily 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) of 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 anlaysis predicted the presence of genes belonging to CYP51 and a plant like CYP710C gene that encodes a plant like sterol C-22 desaturase, a key enzyme in stigmasterol biosynthesis. This is the first report of comparative analysis of the stigmasterol biosynthetic pathway genes of 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 the first comprehensive report on CYPome of Leishmania and molecular evidence of a plant like sterol C-22 desaturase gene in Leishmania.