细菌不饱和脂肪酸合成研究进展

Advances in synthesis of unsaturated fatty acids in bacteria

摘要:

脂肪酸不仅是细菌细胞膜组分，还是许多生物活性物质的合成原料。不饱和脂肪酸(unsaturated fatty acid, UFA)具有更低的相变温度，是细菌调节细胞膜流动性的重要分子，因此UFA合成途径是重要的抗菌药物筛选靶点。细菌可利用厌氧途径合成UFA，其中模式生物大肠杆菌利用经典的FabA-FabB途径合成UFA，但不同细菌中UFA合成的厌氧途径具有多样性，相关催化酶类也不尽相同；细菌还可以利用需氧途径合成UFA，利用脂肪酸脱饱和酶直接将饱和脂肪酸(saturated fatty acid, SFA)转化为不饱和脂肪酸，而不同脱饱和酶会生成不同结构的UFA，在逆境耐受、致病力等多方面发挥重要作用；细菌还可以利用单加氧酶，将脂肪酸合成途径中癸酰酰基载体蛋白(acyl carrier protein, ACP)转化为顺-3-癸烯酰ACP，并最终合成UFA。细菌脂肪酸合成相关的其他酶类在UFA合成或不同种类UFA调节中也发挥着重要作用。本文系统地总结了细菌UFA合成途径与相关酶类的多样性研究进展，旨在为进一步了解细菌UFA合成机制，并以此为靶点开发抗菌药物等方面提供理论支撑。

Abstract:

Fatty acids are not only the components of cell membrane but also the raw materials for the synthesis of bioactive molecules. Unsaturated fatty acids (UFAs) with low phase-transition temperatures are essential molecules for bacteria to regulate cell membrane fluidity. Therefore, the synthetic pathways of UFAs are key targets for the screening of antibacterial agents. Bacteria can adopt the anaerobic pathway to synthesize UFAs. For example, Escherichia coli, a model organism, synthesizes UFAs via the classic FabA-FabB pathway. However, the anaerobic pathways for the synthesis of UFAs vary in different bacteria, and the catalytic enzymes are also different. Bacteria can synthesize UFAs via aerobic pathways, in which fatty acid desaturase directly converts saturated fatty acids (SFAs) into UFAs. Different desaturases introduce double bond to form UFAs with different structures, which play roles in stress responses, pathogenicity and other aspects. Other enzymes involved in the synthesis of fatty acids can also participate in the synthesis of UFAs or regulation of different UFAs. Some bacteria can use monooxygenase to convert capryl-ACP (acyl carrier protein) in the fatty acid synthesis pathway into cis-3-decenyl ACP to synthesize UFAs. We comprehensively reviewed the research progress in the synthesis of UFAs in bacteria, aiming to provide theoretical support for deciphering the mechanism of bacterial synthesis of UFAs and developing the targeted antibacterial drugs.