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Title 

Characterization of tailoring genes involved in the modification of geldanamycin polyketide in Streptomyces hygroscopicus JCM4427

Authors 

J C ShinZ NaD H LeeWon Cheol KimKyeong LeeY M ShenS G PaikYoung-Soo HongJung Joon Lee

Publisher 

The Korean Society for Applied Microbiology

Issue Date 

2008

Citation 

Journal of Microbiology and Biotechnology, vol. 18, no. 6, pp. 1101-1108

Keywords 

geldanamycinpolyketide synthasebacterial genegene expression regulationgenetic complementationgeneticsmolecular geneticsmultigene familystreptomycesgenes, bacterial

Abstract 

Geldanamycin and its analogs are important anticancer agents that inhibit the newly targeted, heat-shock protein (Hsp) 90, which is a chaperone protein in eukaryotic cells. To resolve which geldanamycin biosynthetic genes are responsible for particular post-polyketide synthase (PKS) processing steps and in which order the reactions occur, we individually inactivated candidate genes in Streptomyces hygroscopicus subsp. duamyceticus JCM4427, and isolated and elucidated the structures of intermediates from each mutant. The results indicated that gel7 governs at least one of the benzoquinone ring oxidation steps. In addition, gel16 was found to be involved in double-bond formation between C-4 and C-5 of 4,5-dihydrogeldanamycin, which confirmed our previous findings that this double bond reduced during the post-PKS modification of the polyketide assembly. In addition, pro-geldanamycin, which does not possess a double bond at C-4/5, was purified from the gel7 and 8 double-gene-inactivated mutant.

ISSN 

1017-7825

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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