Inhibition of fungal sphingolipid biosynthesis by rustmicin, galbonolide B and their new 21-hydroxy analogs.
The mode of action of the known antifungal macrolides rustmicin (1) and galbonolide B (2) has been determined to be the inhibition of sphingolipid biosynthesis. A large scale fermentation and isolation process was developed for production of large quantities of rustmicin. New 21-hydroxy derivatives of both compounds were isolated from pilot scale fermentations and were also produced by biotransformation of rustmicin and galbonolide B.
Harris
G H
GH
Department of Natural Products Drug Discovery, Merck Research Laboratories, Rahway, New Jersey 07065, USA.
Shafiee
A
A
Cabello
M A
MA
Curotto
J E
JE
Genilloud
O
O
Göklen
K E
KE
Kurtz
M B
MB
Rosenbach
M
M
Salmon
P M
PM
Thornton
R A
RA
Zink
D L
DL
Mandala
S M
SM
D000935:Antifungal Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002175:Candida / Q000187:drug effects / Q000378:metabolism; D002176:Candida albicans / Q000187:drug effects / Q000378:metabolism; D003455:Cryptococcus neoformans / Q000187:drug effects / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D005285:Fermentation; D005658:Fungi / Q000187:drug effects / Q000378:metabolism*; D007783:Lactones / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D008847:Micromonospora / Q000737:chemistry / Q000378:metabolism; D015394:Molecular Structure; D013107:Sphingolipids / Q000096:biosynthesis*
D000935:Antifungal Agents; D007783:Lactones; D013107:Sphingolipids; C047787:neorustmicin A; C047784:rustmicin