Sterol biosynthesis in Pneumocystis:: unique steps that define unique targets

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 OS 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. (C) 2002 Elsevier Science Ltd. All rights reserved.