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 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.