P450s in Microbial Sterol Biosynthesis and Drug Targets

Colin John Jackson, David Christopher Lamb, Andrew Graham Samuel Warrilow, Josie Elizabeth Parker, Nadja Rodrigues de Melo, Diane Elizabeth Kelly and Steven Lewis Kelly*

Institute of Life Science, School of Medicine, Swansea University, Singleton Park, Swansea SA2 8PP, UK.
Tel: +44 1792 602207; Fax: +44 1792 513430
* Corresponding author: E-mail: s.l.kelly@swansea.ac.uk

The diversity of cytochromes P450s (CYP) in species from various Kingdoms of Life is extensive, sometimes comprising more than 1% of coding genes. Some bacteria do not contain CYP genes while in others, such as the actinomycetes, they are numerous. Microbial eukaryotes usually contain at least CYP51, the ancestral activity needed for sterol 14-demethylation. This CYP exists in some bacteria such as Methylococcus capsulatus and sterol biosynthesis in this methane utilising bacterium is discussed together with CYP51-like proteins of bacteria that have other endogenous functions. In fungi CYP51 is a drug target for azole compounds and here evolution is also occurring to drug resistant forms. Evolutionary aspects of bacterial sterol biosynthesis are discussed.