Mechanistic diversity and regulation of Type II fatty acid synthesis
Mechanistic diversity and regulation of Type II fatty acid synthesis
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DOI：
10.1042/bst0301050
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发表时间：
2002-11-01
影响因子：
3.9
通讯作者：
Rock, CO
中科院分区：
文献类型：
--
作者：
Marrakchi, H;Zhang, YM;Rock, CO
在大多数细菌中，脂肪酸生物合成由一组高度保守的蛋白质催化，称为11型脂肪酸合成酶（FAS）系统。类型11系统组织不同于其哺乳动物对应物，并提供了几个独特的抗菌剂选择性抑制位点。在对11型FAS的遗传学、生物化学和调控的理解方面取得了显着进展。一个重要的进展是发现了脂肪酸降解调节因子FadR和脂肪酸生物合成调节因子FabR在大肠杆菌中不饱和脂肪酸合成的转录控制中的相互作用。基因组序列和高分辨率蛋白质晶体结构的可用性已经扩展了我们对11型FAS的理解，超越了E。coli模型系统对多种病原菌的抑制作用。肺炎链球菌中发现了一种新型烯酰还原酶[烯酰-酰基载体蛋白（ACP）还原酶11，FabK]，枯草芽孢杆菌中存在两种烯酰还原酶（烯酰-ACP还原酶I和111，FabI和FabL），以及在S. pneumoniae（反式-2-顺式-3-烯酰基-ACP异构酶，FabM）。结核分枝杆菌ACP的溶液结构揭示了所有ACP共有的特征，但其扩展的C-末端结构域可能反映了与非常长链中间体的特异性相互作用。
Fatty acid biosynthesis is catalysed in most bacteria by a group of highly conserved proteins known as the Type 11 fatty acid synthase (FAS) system. The Type 11 system organization is distinct from its mammalian counterpart and offers several unique sites for selective inhibition by antibacterial agents. There has been remarkable progress in the understanding of the genetics, biochemistry and regulation of Type 11 FASs. One important advance is the discovery of the interaction between the fatty,T acid degradation regulator, FadR, and the fatty acid biosynthesis regulator, FabR, in the transcriptional control of unsaturated fatty, acid synthesis in Escherichia coli. The availability of genomic :sequences and high-resolution protein crystal structures has expanded our understanding of Type 11 FASs beyond the E. coli model system to a number of pathogens. The molecular diversity, among the pathway enzymes is illustrated by the discovery of a new type of enoyl-reductase in Streptococcus pneumoniae [enoyl-acyl carrier protein (ACP) reductase 11, FabK], the presence of two enoyl-reductases in Bacillus subtilis (enoyl-ACP reductases I and 111, FabI and FabL), and the use of a new mechanism for unsaturated fatty acid formation in S. pneumoniae (trans-2-cis-3-enoyl-ACP isomerase, FabM). The solution structure of ACP from Mycobacterium tuberculosis revealed features common to all ACPs, but its extended C-terminal domain may reflect a specific interaction with very-long-chain intermediates.