title: Inhibition of fungal sphingolipid biosynthesis by rustmicin, galbonolide B and their new 21-hydroxy analogs.
abstract: 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.
authors.affiliation: Department of Natural Products Drug Discovery, Merck Research Laboratories, Rahway, New Jersey 07065, USA.
authors.forename: G H
authors.initials: GH
authors.lastname: Harris
authors.forename: A
authors.initials: A
authors.lastname: Shafiee
authors.forename: M A
authors.initials: MA
authors.lastname: Cabello
authors.forename: J E
authors.initials: JE
authors.lastname: Curotto
authors.forename: O
authors.initials: O
authors.lastname: Genilloud
authors.forename: K E
authors.initials: KE
authors.lastname: Göklen
authors.forename: M B
authors.initials: MB
authors.lastname: Kurtz
authors.forename: M
authors.initials: M
authors.lastname: Rosenbach
authors.forename: P M
authors.initials: PM
authors.lastname: Salmon
authors.forename: R A
authors.initials: RA
authors.lastname: Thornton
authors.forename: D L
authors.initials: DL
authors.lastname: Zink
authors.forename: S M
authors.initials: SM
authors.lastname: Mandala
mesh_terms: 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*
chemical_list: D000935:Antifungal Agents; D007783:Lactones; D013107:Sphingolipids; C047787:neorustmicin A; C047784:rustmicin