title: Isolation and characterization of novel geldanamycin analogues.
abstract: New geldanamycin analogues with novel structures arising from direct microbial bioconversion and a genetically engineered geldanamycin producer were isolated and characterized. Three compounds, 15-hydroxygeldanamycin, a tricyclic geldanamycin analog (KOSN-1633), and methyl-geldanamycinate), were isolated after geldanamycin was added to a growing culture of the herbimycin producing strain-Streptomyces hygroscopicus AM-3672. Two related compounds, 17-formyl-17-demethoxy-18-O,-21-O-dihydrogeldanamycin and 17-hydroxymethyl-17-demethoxygeldanamycin were isolated from S. hygroscopicus NRRL 3602/pKOS279-78, a geldanamycin-producing strain containing various genes isolated from S. hygroscopicus AM-3672. Compared with geldanamycin, these five new compounds exhibited reduced cytotoxicity against SKBr3 cancer cells.
authors.affiliation: Kosan Biosciences, Inc., 3832 Bay Center Place Hayward, CA 94545 USA. hu@Kosan.com
authors.forename: Zhihao
authors.initials: Z
authors.lastname: Hu
authors.forename: Yaoquan
authors.initials: Y
authors.lastname: Liu
authors.forename: Zong-Qiang
authors.initials: ZQ
authors.lastname: Tian
authors.forename: Wei
authors.initials: W
authors.lastname: Ma
authors.forename: Courtney M
authors.initials: CM
authors.lastname: Starks
authors.forename: Rika
authors.initials: R
authors.lastname: Regentin
authors.forename: Peter
authors.initials: P
authors.lastname: Licari
authors.forename: David C
authors.initials: DC
authors.lastname: Myles
authors.forename: C Richard
authors.initials: CR
authors.lastname: Hutchinson
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000302:isolation & purification* / Q000494:pharmacology; D016227:Benzoquinones; D045744:Cell Line, Tumor; D006801:Humans; D047029:Lactams, Macrocyclic; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D011809:Quinones / Q000378:metabolism* / Q000494:pharmacology; D013302:Streptomyces / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000903:Antibiotics, Antineoplastic; D016227:Benzoquinones; D047029:Lactams, Macrocyclic; D011809:Quinones; C001277:geldanamycin