非典型聚酮合成酶-非核糖体肽合成酶杂合体参与甾醇- c4 -甲基氧化酶抑制剂PF1163A的生物合成

IF 4.7 1区化学 Q1 CHEMISTRY, ORGANIC Organic Letters Pub Date : 2024-12-24 DOI:10.1021/acs.orglett.4c03675

Qiaolin Ji, Xingxing Wei, Shengkun Liu, Yudai Matsuda

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引用次数: 0

摘要

PF1163A(1)是一种抑制甾醇- c4 -甲基氧化酶的真菌代谢物。本研究通过异源表达实验，鉴定了1的生物合成基因簇，并阐明了其生物合成途径。聚酮合成酶-非核糖体合成酶杂合体PfaA，负责PF1163A的生物合成，具有不寻常的结构域组织，具有串联缩合(C)结构域和末端缩合结构域。诱变研究表明，两个C结构域都是PfaA功能所必需的。

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Involvement of a Noncanonical Polyketide Synthase–Nonribosomal Peptide Synthetase Hybrid in the Biosynthesis of Sterol-C4-methyl Oxidase Inhibitor PF1163A

PF1163A (1) is a fungal metabolite that inhibits sterol-C4-methyl oxidase. In this study, we identified the biosynthetic gene cluster of 1 and elucidated its biosynthetic pathway through heterologous expression experiments. Polyketide synthase–nonribosomal synthetase hybrid PfaA, which is responsible for the biosynthesis of PF1163A, harbors an unusual domain organization with tandem condensation (C) domains and a terminal condensation domain. Mutagenesis studies suggest that both C domains are required for the function of PfaA.

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来源期刊

Organic Letters 化学-有机化学

CiteScore

9.30

自引率

11.50%

发文量

1607

审稿时长

1.5 months

期刊介绍： Organic Letters invites original reports of fundamental research in all branches of the theory and practice of organic, physical organic, organometallic,medicinal, and bioorganic chemistry. Organic Letters provides rapid disclosure of the key elements of significant studies that are of interest to a large portion of the organic community. In selecting manuscripts for publication, the Editors place emphasis on the originality, quality and wide interest of the work. Authors should provide enough background information to place the new disclosure in context and to justify the rapid publication format. Back-to-back Letters will be considered. Full details should be reserved for an Article, which should appear in due course.