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

Jin Chul Shin, Zhu Na, Dongho Lee, Woncheol Kim, Kyeong Lee, Yue Mao Shen, Sang Gi Paik, Young Soo Hong, Jung Joon Lee

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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. The 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 is 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 gel8 double-gene-inactivated mutant.

Original languageEnglish
Pages (from-to)1101-1108
Number of pages8
JournalJournal of Microbiology and Biotechnology
Volume18
Issue number6
Publication statusPublished - 2008 Jun 1

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Keywords

  • Biosynthesis
  • Geldanamycin
  • Polyketide
  • Streptomyces

ASJC Scopus subject areas

  • Biotechnology
  • Applied Microbiology and Biotechnology

Cite this

Shin, J. C., Na, Z., Lee, D., Kim, W., Lee, K., Shen, Y. M., Paik, S. G., Hong, Y. S., & Lee, J. J. (2008). Characterization of tailoring genes involved in the modification of geldanamycin polyketide in Streptomyces hygroscopicus JCM4427. Journal of Microbiology and Biotechnology, 18(6), 1101-1108.