Identification of 4,5-Dihydro-4-hydroxygeldanamycins
As Shunt Products of Geldanamycin Biosynthesis

Li, Ting; Ni, Siyang; Jia, Changhong; Wang, Hongyuan; Sun, Guizhi; Wu, Linzhuan; Gan, Maoluo; Shan, Guangzhi; He, Weiqing; Lin, Ling; Zhou, Hongxia; Wang, Yiguang

doi:10.1021/np3001738.s001

np3001738_si_001.pdf (3.76 MB)

Identification of 4,5-Dihydro-4-hydroxygeldanamycins As Shunt Products of Geldanamycin Biosynthesis

journal contribution

posted on 2012-08-24, 00:00 authored by Ting Li, Siyang Ni, Changhong Jia, Hongyuan Wang, Guizhi Sun, Linzhuan Wu, Maoluo Gan, Guangzhi Shan, Weiqing He, Ling Lin, Hongxia Zhou, Yiguang Wang

Two new geldanamycin (GDM) analogues, (4S)-4,5-dihydro-4-hydroxygeldanamycin (1) and (4R)-4,5-dihydro-4-hydroxygeldanamycin (2), were identified from Streptomyces hygroscopicus 17997. Compounds 1 and 2 were not normal intermediates of GDM biosynthesis but shunt products of C-4,5 oxidation catalyzed by GdmP, a cytochrome P450 oxidase acting as a desaturase in GDM biosynthesis. Preliminary assays implied that, compared with GDM, 1 and 2 exhibited decreased cytotoxicity.