Organization of the Biosynthetic Gene Cluster for the Polyketide Antitumor Macrolide, Pladienolide, in Streptomyces platensis Mer-11107
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概要
- 論文の詳細を見る
Pladienolides are novel 12-membered macrolides produced by Streptomyces platensis Mer-11107. They show strong antitumor activity and are a potential lead in the search for novel antitumor agents. We sequenced the 65-kb region covering the biosynthetic gene cluster, and found four polyketide synthase genes (pldAI-pldAIV) composed of 11 modules, three genes involved in post-modifications (pldB-D), and a luxR-family regulatory gene (pldR). The thioesterase domain of pldAIV was more dissimilar to that of polyketide synthase systems synthesizing 12/14-membered macrolide polyketides than to that of systems synthesizing other cyclic polyketides. The pldB gene was identified as a 6-hydroxylase belonging to a cytochrome P450 of the CYP107 family. This was clarified by a disruption experiment on pldB, in which the disruptant produced 6-dehydroxy pladienolide B. Two genes located downstream of pldB, designated pldC and pldD, are thought to be a probable genes for 7-O-acetylase and 18, 19-epoxydase respectively.
- 2008-11-23
著者
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Ikeda Haruo
Kitasato Institute For Life Sciences & Graduate School Of Infection Control Kitasato University
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YOSHIDA MASASHI
Bioresource Laboratories, Mercian Corp.
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Arisawa Akira
Bioresource Laboratories Mercian Corp.
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ARITOKU Yasuhide
Bioresource Laboratories, Mercian Corp.
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Tsuchida Toshio
Bioresource Laboratories Mercian Corp.
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MACHIDA Kazuhiro
Bioresource Laboratories, Mercian Corp.
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Ikeda Haruo
Kitasato Institute For Life Sciences And Graduate School Of Infection Control Kitasato University
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TAKEDA Susumu
Bioresource Laboratories, Mercian Corporation
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Aritoku Yasuhide
Bioresource Laboratories Mercian Corp.
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Takeda Susumu
Bioresource Laboratories Mercian Corporation
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Machida Kazuhiro
Bioresource Laboratories Mercian Corp.
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Yoshida Masashi
Bioresource Laboratories Mercian Corporation
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Yoshida Masashi
Bioresource Laboratories Mercian Corp.
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