Kazuhiro Machida, Yasuhide Aritoku, Takashi Nakashima, Akira Arisawa, Toshio Tsuchida
Bioresource Laboratories, Mercian Corp, Iwata, Shizuoka, Japan. machida-k@mercian.co.jp
Journal of bioscience and bioengineering 2008 JunPladienolide B and its 16-hydroxylated derivative (pladienolide D) are novel 12-membered macrolides produced by Streptomyces platensis Mer-11107 showing strong in vitro and in vivo antitumor activity. While pladienolide B is mainly produced by this strain, pladienolide D is produced to a lesser extent. To facilitate the production of pladienolide D by biotransformation, we found that Streptomyces bungoensis A-1544 was able to hydroxylate pladienolide B at 16-position. We identified psmA from S. bungoensis A-1544, which encoded a pladienolide B 16-hydroxylase PsmA belonging to the CYP105 family of cytochrome P450. To increase the efficiency of pladienolide D production, we constructed recombinant S. bungoensis A-1544 overexpressing psmA and performed biotransformation of pladienolide B to pladienolide D. This biotransformation achieved a production level 15-fold higher than that using the control strain S. bungoensis A-1544/pIJ702.
Kazuhiro Machida, Yasuhide Aritoku, Takashi Nakashima, Akira Arisawa, Toshio Tsuchida. Increase in pladienolide D production rate using a Streptomyces strain overexpressing a cytochrome P450 gene. Journal of bioscience and bioengineering. 2008 Jun;105(6):649-54
PMID: 18640605
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