*3.2. CYP Mining and Annotation*

Genome mining for CYPs and subsequent annotation was carried out following the protocol described elsewhere [36,38,53,54]. Briefly, proteomes cryptococcal species from different genome databases, listed in Section 3.1, were downloaded and subjected to an NCBI conserved domain search [55] to classify the proteins into different subfamilies. The proteins grouped under a CYP superfamily were selected and subjected to blast analysis against fungal CYPs [42] to identify homolog CYPs. Based on percentage identity with a named homolog CYP, the hit proteins were then assigned to different CYP families and CYP subfamilies, following the International P450 Nomenclature Committee rule, that is, >40% identity for a family and >55% identity for a subfamily [40,41]. CYPs that had less than 40% identity with named fungal CYPs [42] were assigned to a new family. For each species, CYPs from different databases were compared and duplicate CYPs were removed from the final CYP count.
