Identification of 4,5-dihydro-4-hydroxygeldanamycins as shunt products of geldanamycin biosynthesis

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

doi:10.1021/np3001738

Identification of 4,5-dihydro-4-hydroxygeldanamycins as shunt products of geldanamycin biosynthesis

J Nat Prod. 2012 Aug 24;75(8):1480-4. doi: 10.1021/np3001738. Epub 2012 Jul 31.

Authors

Ting Li¹, Siyang Ni, Changhong Jia, Hongyuan Wang, Guizhi Sun, Linzhuan Wu, Maoluo Gan, Guangzhi Shan, Weiqing He, Ling Lin, Hongxia Zhou, Yiguang Wang

Affiliation

¹ 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.

PMID: 22849774
DOI: 10.1021/np3001738

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Benzoquinones* / chemistry
Benzoquinones* / metabolism
Benzoquinones* / pharmacology
Lactams, Macrocyclic* / chemistry
Lactams, Macrocyclic* / metabolism
Lactams, Macrocyclic* / pharmacology
Molecular Structure
NADPH-Ferrihemoprotein Reductase / metabolism*
Nuclear Magnetic Resonance, Biomolecular
Oxidation-Reduction
Streptomyces / chemistry*
Streptomyces / genetics
Streptomyces / metabolism

Substances

(4S)-4,5-dihydro-4-hydroxygeldanamycin
Benzoquinones
Lactams, Macrocyclic
NADPH-Ferrihemoprotein Reductase
geldanamycin