Isolation and characterization of novel geldanamycin analogues.
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.
Hu
Zhihao
Z
Kosan Biosciences, Inc., 3832 Bay Center Place Hayward, CA 94545 USA. hu@Kosan.com
Liu
Yaoquan
Y
Tian
Zong-Qiang
ZQ
Ma
Wei
W
Starks
Courtney M
CM
Regentin
Rika
R
Licari
Peter
P
Myles
David C
DC
Hutchinson
C Richard
CR
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
D000903:Antibiotics, Antineoplastic; D016227:Benzoquinones; D047029:Lactams, Macrocyclic; D011809:Quinones; C001277:geldanamycin