title: Sterol biosynthesis in Pneumocystis: unique steps that define unique targets.
abstract: Pneumocystis lacks ergosterol, and several antimycotics that bind ergosterol in fungal membranes or inhibit its synthesis are ineffective against Pneumocystis pneumonia. The organism synthesizes C(28) and C(29) Delta(7) 24-alkylsterols, 24-alkyllanosterol derivatives, and Delta(5) 24-alkylsterols, which may be produced by modifying scavenged Delta(5) sterols. Mammals cannot desaturate C-22 and alkylate C-24 of sterols, thus, these processes are particularly attractive targets for antifungal drug development. Recent data indicate that C-22 desaturation is not, but C-24 alkylation is an attractive target in P. carinii. The P. carinii S-adenosyl-L-methionine:sterol C-24 methyl transferase (SAM:SMT) has unique properties; it prefers lanosterol as its sterol substrate.
authors.affiliation: Department of Biological Sciences, University of Cincinnati, OH 45221, USA. edna.kaneshiro@uc.edu
authors.forename: Edna S
authors.initials: ES
authors.lastname: Kaneshiro
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D011010:Pneumocystis / Q000187:drug effects* / Q000378:metabolism*; D013261:Sterols / Q000096:biosynthesis* / Q000737:chemistry
chemical_list: D000935:Antifungal Agents; D013261:Sterols