区域间配位决定了UK-2A生物合成中聚酮扩展剂单元的特异性。

IF 2.6 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
ChemBioChem Pub Date : 2025-03-27 DOI:10.1002/cbic.202401050
Mengmeng Zheng, Wan Zhang, Zhi Lin, Lei Li, Zixin Deng, Xudong Qu
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引用次数: 0

摘要

控制扩展单元的加入是操纵聚酮支架的关键策略。目前的认识表明,模块化聚酮合成酶(PKS)的延伸剂单元结合主要受酰基转移酶(AT)结构域以及酮合成酶(KS)、酮还原酶(KR)和硫酯酶(TE)结构域的调节。在这项研究中,我们在体内和体外研究了UK-2A在C7位置特异性结合苯基侧链的机制。我们的研究结果表明,苯丙二酰辅酶a扩展单元的结合是由整个PKS模块的结构域间协调控制的,而不是由单个结构域控制的。这些结果挑战了以前的认识,并为未来的聚酮工程提供了新的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Interdomain Coordination Determines Polyketide Extender Unit Specificity in UK-2A Biosynthesis.

Controlling the incorporation of extender units is a key strategy for manipulating polyketide scaffolds. Current understanding suggests that extender unit incorporation by modular polyketide synthase (PKS) is primarily regulated by acyltransferase domains, along with ketosynthase, ketoreductase, and thioesterase domains. In this study, the mechanism is investigated underlying the specific incorporation of the benzyl side chain at the C7 position of UK-2A, both in vivo and in vitro. These findings reveal that the incorporation of the benzylmalonyl-CoA extender unit is governed by interdomain coordination across the entire PKS module, rather than being controlled by individual domains. These results challenge previous recognition and offer new insights for the future engineering of polyketides.

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来源期刊
ChemBioChem
ChemBioChem 生物-生化与分子生物学
CiteScore
6.10
自引率
3.10%
发文量
407
审稿时长
1 months
期刊介绍: ChemBioChem (Impact Factor 2018: 2.641) publishes important breakthroughs across all areas at the interface of chemistry and biology, including the fields of chemical biology, bioorganic chemistry, bioinorganic chemistry, synthetic biology, biocatalysis, bionanotechnology, and biomaterials. It is published on behalf of Chemistry Europe, an association of 16 European chemical societies, and supported by the Asian Chemical Editorial Society (ACES).
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