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酰基载体蛋白(ACPs)如何指导脂肪酸和聚酮化合物生物合成。

How Acyl Carrier Proteins (ACPs) Direct Fatty Acid and Polyketide Biosynthesis.

机构信息

Institute of Organic Chemistry and Chemical Biology, Buchmann Institute for Molecular Life Sciences, Goethe University Frankfurt, Max-von-Laue-Str. 15, 60438, Frankfurt am Main, Germany.

出版信息

Angew Chem Int Ed Engl. 2024 Jan 22;63(4):e202312476. doi: 10.1002/anie.202312476. Epub 2023 Nov 21.

Abstract

Megasynthases, such as type I fatty acid and polyketide synthases (FASs and PKSs), are multienzyme complexes responsible for producing primary metabolites and complex natural products. Fatty acids (FAs) and polyketides (PKs) are built by assembling and modifying small acyl moieties in a stepwise manner. A central aspect of FA and PK biosynthesis involves the shuttling of substrates between the domains of the multienzyme complex. This essential process is mediated by small acyl carrier proteins (ACPs). The ACPs must navigate to the different catalytic domains within the multienzyme complex in a particular order to guarantee the fidelity of the biosynthesis pathway. However, the precise mechanisms underlying ACP-mediated substrate shuttling, particularly the factors contributing to the programming of the ACP movement, still need to be fully understood. This Review illustrates the current understanding of substrate shuttling, including concepts of conformational and specificity control, and proposes a confined ACP movement within type I megasynthases.

摘要

巨合酶,如 I 型脂肪酸和聚酮合酶(FAS 和 PKS),是负责产生初级代谢物和复杂天然产物的多酶复合物。脂肪酸(FAs)和聚酮(PKs)是通过逐步组装和修饰小酰基片段构建的。FA 和 PK 生物合成的一个核心方面涉及多酶复合物的域之间的底物穿梭。这个基本过程由小酰基辅酶 A 蛋白(ACP)介导。ACP 必须按照特定的顺序导航到多酶复合物的不同催化域,以保证生物合成途径的保真度。然而,ACP 介导的底物穿梭的确切机制,特别是导致 ACP 运动编程的因素,仍需要充分理解。这篇综述说明了目前对底物穿梭的理解,包括构象和特异性控制的概念,并提出了 I 型巨合酶中受限的 ACP 运动。

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