Identification and Characterization of the Chaetoviridin and Chaetomugilin Gene Cluster in Chaetomium globosum Reveal Dual Functions of an Iterative Highly-Reducing Polyketide Synthase

Identification and Characterization of the Chaetoviridin and Chaetomugilin Gene Cluster in Chaetomium globosum Reveal Dual Functions of an Iterative Highly-Reducing Polyketide Synthase
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DOI:
10.1021/ja3090498
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发表时间:
2012-10-31
影响因子:
15
通讯作者:
Watanabe, Kenji
Watanabe, Kenji
中科院分区:
化学1区
文献类型:
--
作者:
Winter, Jaclyn M.;Sato, Michio;Watanabe, Kenji

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我们报告了来自球毛壳菌 (Chaetomium globosum) 的 caz 生物合成簇的鉴定和表征,以及高度还原性聚酮合酶 (PKS) 的表征,该酶以顺序和收敛方式与非还原性 PKS 一起作用,形成毛壳菌素 (chaetomugilin) 和毛壳病毒素 azaphilones。基因失活研究证实了单个 caz 基因参与阿扎菲酮生物合成。通过体外重构,我们证明了使用高度还原性 PKS 和酰基转移酶从吡喃醌中间体 cazisochromene 体外合成毛壳病毒素 A。
We report the identification and characterization of the caz biosynthetic cluster from Chaetomium globosum and the characterization of a highly reducing polyketide synthase (PKS) that acts in both a sequential and convergent manner with a nonreducing PKS to form the chaetomugilin and chaetoviridin azaphilones. Genetic inactivation studies verified the involvement of individual caz genes in the biosynthesis of the azaphilones. Through in vitro reconstitution, we demonstrated the in vitro synthesis of chaetoviridin A from the pyranoquinone intermediate cazisochromene using the highly reducing PKS and an acyltransferase.