title: Platensimycin and platencin congeners from Streptomyces platensis.
abstract: Platensimycin (1a) and platencin (2) are inhibitors of FabF and FabF/H bacterial fatty acid synthase. The discovery of natural congeners is an approach that can render a better understanding of the structure-function relationships of complex natural products. The isolation and structure elucidation of nine new congeners (11-20) of platensimycin and platencin are described from a fermentation broth of Streptomyces platensis. These hydroxylated congeners are likely derived by cytochrome P450 oxidation of the terpenoid units post-cyclization. Polar groups in the terpenoid portion of the molecule produce negative interactions with the hydrophobic pocket of FabF, resulting in poor activities. However, the discovery of these compounds serves an important purpose, not only to understand structure-function relationships, which cannot be easily accessed by chemical modification, but also to provide access to compounds that could be used for structural identification/confirmation of the oxidative trace metabolites produced in vivo during animal experiments.
authors.affiliation: Merck Research Laboratories, Rahway, New Jersey 07065, USA.
authors.forename: Chaowei
authors.initials: C
authors.lastname: Zhang
authors.forename: John
authors.initials: J
authors.lastname: Ondeyka
authors.forename: Kithsiri
authors.initials: K
authors.lastname: Herath
authors.forename: Hiranthi
authors.initials: H
authors.lastname: Jayasuriya
authors.forename: Ziqiang
authors.initials: Z
authors.lastname: Guan
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Zink
authors.forename: Lisa
authors.initials: L
authors.lastname: Dietrich
authors.forename: Bruce
authors.initials: B
authors.lastname: Burgess
authors.forename: Sookhee N
authors.initials: SN
authors.lastname: Ha
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Sheo B
authors.initials: SB
authors.lastname: Singh
mesh_terms: D000218:Adamantane / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D062365:Aminobenzoates / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D000627:Aminophenols / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D000813:Anilides / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D054889:Fatty Acid Synthase, Type II / Q000037:antagonists & inhibitors; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011083:Polycyclic Compounds / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D013237:Stereoisomerism; D013302:Streptomyces / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D062365:Aminobenzoates; D000627:Aminophenols; D000813:Anilides; D000900:Anti-Bacterial Agents; D011083:Polycyclic Compounds; D003577:Cytochrome P-450 Enzyme System; D054889:Fatty Acid Synthase, Type II; D000218:Adamantane; C510909:platensimycin; C520340:platencin