Phylogeny, evolution, and potential ecological relationship of cytochrome CYP52 enzymes in Saccharomycetales yeasts.

Cytochrome P450s from the CYP52 family participate in the assimilation of alkanes and fatty acids in fungi. In this work, the evolutionary history of a set of orthologous and paralogous CYP52 proteins from Saccharomycetales yeasts was inferred. Further, the phenotypic assimilation profiles were related with the distribution of cytochrome CYP52 members among species. The maximum likelihood phylogeny of CYP52 inferred proteins reveled a frequent ancient and modern duplication and loss events that generated orthologous and paralogous groups. Phylogeny and assimilation profiles of alkanes and fatty acids showed a family expansion in yeast isolated from hydrophobic-rich environments. Docking analysis of deduced ancient CYP52 proteins suggests that the most ancient function was the oxidation of C4-C11 alkanes, while the oxidation of >10 carbon alkanes and fatty acids is a derived character. The ancient CYP52 paralogs displayed partial specialization and promiscuous interaction with hydrophobic substrates. Additionally, functional optimization was not evident. Changes in the interaction of ancient CYP52 with different alkanes and fatty acids could be associated with modifications in spatial orientations of the amino acid residues that comprise the active site. The extended family of CYP52 proteins is likely evolving toward functional specialization, and certain redundancy for substrates is being maintained.