Increase in pladienolide D production rate using a Streptomyces strain overexpressing a cytochrome P450 gene.
Pladienolide 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.
Machida
Kazuhiro
K
Bioresource Laboratories, Mercian Corp, Iwata, Shizuoka, Japan. machida-k@mercian.co.jp
Aritoku
Yasuhide
Y
Nakashima
Takashi
T
Arisawa
Akira
A
Tsuchida
Toshio
T
D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism*; D004852:Epoxy Compounds / Q000378:metabolism*; D005818:Genetic Engineering / Q000379:methods*; D018942:Macrolides / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011994:Recombinant Proteins / Q000378:metabolism; D013302:Streptomyces / Q000235:genetics* / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics
D004852:Epoxy Compounds; D018942:Macrolides; D011994:Recombinant Proteins; C522342:pladienolide B; D003577:Cytochrome P-450 Enzyme System