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KMID : 0545120080180061101
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Journal of Microbiology and Biotechnology
2008 Volume.18 No. 6 p.1101 ~ p.1108
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Characterization of Tailoring Genes Involved in the Modification of Geldanamycin Polyketide in Streptomyces hygroscopicus JCM4427
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Shin Jin-Chul
Na Zhu
Lee Dong-Ho
Kim Won-Cheol
Lee Kyeong
Shen Yue-Mao
Paik Sang-Gi
Hong Young-Soo
Lee Jung-Joon
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Abstract
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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.
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KEYWORD
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Geldanamycin, biosynthesis, Streptomyces, polyketide
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