Evolutionary insights into the selectivity of sterol oxidising cytochrome P450 enzymes based on ancestral sequence reconstruction.

ABSTRACT: The cytochrome P450 (CYP) enzyme CYP125A1 is a crucial enzyme for the long-term survival and pathogenicity of Mycobacterium tuberculosis. CYP125 genes are found not only in pathogenic mycobacteria but are also widely dispersed within the Actinobacteria phylum, with many species possessing multiple copies of CYP125 encoding genes. Their primary function is the catalytic hydroxylation of the terminal methyl group of cholesterol and phytosterols. We have previously shown that CYP125 enzymes from distinct mycobacteria have substrate selectivity preferences for animal versus plant steroid oxidation. An evolutionary understanding of this selectivity is not known. Here, we use Ancestral Sequence Reconstruction (ASR), to support the hypothesis that some CYP125 enzymes evolved in a ma

SUBMITTER: Doherty DZ 

PROVIDER: S-EPMC12100521 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature