title: Identification of 4,5-dihydro-4-hydroxygeldanamycins as shunt products of geldanamycin biosynthesis.
abstract: 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.
authors: Key Laboratory of Biotechnology of Antibiotics of Ministry of Health, Institute of Medicinal Biotechnology, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, People's Republic of China.
authors: Ting
authors: T
authors: Li
authors: Siyang
authors: S
authors: Ni
authors: Changhong
authors: C
authors: Jia
authors: Hongyuan
authors: H
authors: Wang
authors: Guizhi
authors: G
authors: Sun
authors: Linzhuan
authors: L
authors: Wu
authors: Maoluo
authors: M
authors: Gan
authors: Guangzhi
authors: G
authors: Shan
authors: Weiqing
authors: W
authors: He
authors: Ling
authors: L
authors: Lin
authors: Hongxia
authors: H
authors: Zhou
authors: Yiguang
authors: Y
authors: Wang
mesh_terms: D016227:Benzoquinones / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D047029:Lactams, Macrocyclic / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D015394:Molecular Structure; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism*; D019906:Nuclear Magnetic Resonance, Biomolecular; D010084:Oxidation-Reduction; D013302:Streptomyces / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: C576023:(4S)-4,5-dihydro-4-hydroxygeldanamycin; D016227:Benzoquinones; D047029:Lactams, Macrocyclic; D009251:NADPH-Ferrihemoprotein Reductase; C001277:geldanamycin