Cyclopropane ring formation in membrane lipids of bacteria
Cyclopropane ring formation in membrane lipids of bacteria
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DOI：
10.1128/mmbr.61.4.429-441.1997
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发表时间：
1997-12
影响因子：
12.9
通讯作者：
D. Grogan;J. Cronan
中科院分区：
文献类型：
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作者：
D. Grogan;J. Cronan
几十年来，人们已经知道环丙烷脂肪酸（CFAs）存在于许多细菌的磷脂中。CFAs是通过在不饱和脂肪酸（UFAs）的碳-碳双键上加成一个亚甲基而形成的，亚甲基来自s -腺苷蛋氨酸的甲基。C1转移不涉及游离脂肪酸或磷脂生物合成的中间体，而是已经结合到膜双层中的成熟磷脂分子。此外，CFAs通常在细菌培养的固定阶段开始时产生。因此，CFA的形成可以被认为是细菌膜脂双分子层有条件的合成后修饰。这一修改在几个方面值得注意。它由一种可溶性酶催化，尽管其中一种底物UFA双键通常深藏在磷脂双分子层的疏水内部。CFA合成酶能够区分只含有饱和脂肪酸的磷脂囊泡和不饱和脂肪酸的磷脂囊泡；它对前一种成分的囊泡没有亲和力。这些和其他性质意味着在生物合成CFAs过程中发生了拓扑结构新颖的蛋白质-脂质相互作用。批量培养中ufa到CFA转化的时间和程度以及CFA合成在细菌中的广泛分布似乎表明这一现象具有重要的生理作用，尽管对各种假设进行了实验测试，但其原理仍不清楚。然而，通过遗传方法操作大肠杆菌的CFA合成酶为CFA形成的生理学提供了有价值的见解。它已经鉴定出CFA合酶基因是大肠杆菌中几个rpos调控基因之一，并为构建菌株提供了条件，从而可以适当地评估CFAs的细胞功能。CFA合酶结构基因的克隆和操作也使这种新颖但极不稳定的酶能够从分子角度进行纯化和分析，并导致在临床上重要的细菌病原体中鉴定出机制相关的酶。
It has been known for several decades that cyclopropane fatty acids (CFAs) occur in the phospholipids of many species of bacteria. CFAs are formed by the addition of a methylene group, derived from the methyl group of S-adenosylmethionine, across the carbon-carbon double bond of unsaturated fatty acids (UFAs). The C1 transfer does not involve free fatty acids or intermediates of phospholipid biosynthesis but, rather, mature phospholipid molecules already incorporated into membrane bilayers. Furthermore, CFAs are typically produced at the onset of the stationary phase in bacterial cultures. CFA formation can thus be considered a conditional, postsynthetic modification of bacterial membrane lipid bilayers. This modification is noteworthy in several respects. It is catalyzed by a soluble enzyme, although one of the substrates, the UFA double bond, is normally sequestered deep within the hydrophobic interior of the phospholipid bilayer. The enzyme, CFA synthase, discriminates between phospholipid vesicles containing only saturated fatty acids and those containing UFAs; it exhibits no affinity for vesicles of the former composition. These and other properties imply that topologically novel protein-lipid interactions occur in the biosynthesis of CFAs. The timing and extent of the UFA-to-CFA conversion in batch cultures and the widespread distribution of CFA synthesis among bacteria would seem to suggest an important physiological role for this phenomenon, yet its rationale remains unclear despite experimental tests of a variety of hypotheses. Manipulation of the CFA synthase of Escherichia coli by genetic methods has nevertheless provided valuable insight into the physiology of CFA formation. It has identified the CFA synthase gene as one of several rpoS-regulated genes of E. coli and has provided for the construction of strains in which proposed cellular functions of CFAs can be properly evaluated. Cloning and manipulation of the CFA synthase structural gene have also enabled this novel but extremely unstable enzyme to be purified and analyzed in molecular terms and have led to the identification of mechanistically related enzymes in clinically important bacterial pathogens.