Fatty acid biosynthesis in actinomycetes.

Fatty acid biosynthesis in actinomycetes.
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DOI:
10.1111/j.1574-6976.2010.00259.x
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发表时间:
2011-05
影响因子:
11.3
通讯作者:
Gramajo H
Gramajo H
中科院分区:
生物学1区
文献类型:
--
作者:
Gago G;Diacovich L;Arabolaza A;Tsai SC;Gramajo H

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所有产生脂肪酸的生物都是通过一个重复的反应循环来实现的。在哺乳动物和其他动物中,这些反应是由I型脂肪酸合酶(FAS)催化的,这是一种大型的多功能蛋白质,生长的脂肪酸链与之共价连接。相比之下,大多数细菌(和植物)含有II型系统,其中每个反应由一种独立的蛋白质催化。大肠杆菌中脂肪酸生物合成的途径已经明确,并且为阐明其他细菌中的II型FAS途径奠定了基础。然而,放线菌门中的脂肪酸生物合成更加多样化:分枝杆菌同时拥有两种FAS系统,而链霉菌属仅具有多酶的FAS II系统,棒状杆菌属则仅有FAS I系统。在这篇综述中,我们概述了上述三个放线菌属中两种FAS系统的基因组结构、生化特性和生理相关性。我们还详细阐述了酰基辅酶A羧化酶(ACCase)的生化和结构特性,该酶催化放线菌中脂肪酸合成的第一个关键步骤,并讨论了其底物特异性的分子基础以及基于结构鉴定具有抗分枝杆菌特性的新型ACCase抑制剂。
All organisms that produce fatty acids do so via a repeated cycle of reactions. In mammals and other animals, these reactions are catalyzed by a type I fatty acid synthase (FAS), a large multifunctional protein to which the growing chain is covalently attached. In contrast, most bacteria (and plants) contain a type II system in which each reaction is catalyzed by a discrete protein. The pathway of fatty acid biosynthesis in Escherichia coli is well established and has provided a foundation for elucidating the type II FAS pathways in other bacteria. However, fatty acid biosynthesis is more diverse in the phylum Actinobacteria: Mycobacterium, possess both FAS systems while Streptomyces species have only the multi-enzyme FAS II system and Corynebacterium species exclusively FAS I. In this review we present an overview of the genome organization, biochemical properties and physiological relevance of the two FAS systems in the three genera of actinomycetes mentioned above. We also address in detail the biochemical and structural properties of the acyl-CoA carboxylases (ACCases) that catalyzes the first committed step of fatty acid synthesis in actinomycetes, and discuss the molecular bases of their substrate specificity and the structure-based identification of new ACCase inhibitors with anti-mycobacterial properties.
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