College of Life Sciences, Shandong Agricultural University, Taian, Shandong, China.
Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
mBio. 2019 May 7;10(3):e00577-19. doi: 10.1128/mBio.00577-19.
Acyl carrier proteins (ACPs) play essential roles in the synthesis of fatty acids and transfer of long fatty acyl chains into complex lipids. The genome contains two annotated genes, called and AcpA is encoded within the fatty acid synthesis (fab) operon and appears essential. In contrast, AcpB is an atypical ACP, having only 30% residue identity with AcpA, and is not essential. Deletion of has no effect on growth or fatty acid synthesis in media lacking fatty acids. However, unlike the wild-type strain, where growth with oleic acid resulted in almost complete blockage of fatty acid synthesis, the strain largely continued fatty acid synthesis under these conditions. Blockage in the wild-type strain is due to repression of operon transcription, leading to levels of fatty acid synthetic proteins (including AcpA) that are insufficient to support synthesis. Transcription of the operon is regulated by FabT, a repressor protein that binds DNA only when it is bound to an acyl-ACP ligand. Since AcpA is encoded in the operon, its synthesis is blocked when the operon is repressed and thus cannot provide a stable supply of ACP for synthesis of the acyl-ACP ligand required for DNA binding by FabT. In contrast to AcpA, transcription is unaffected by growth with exogenous fatty acids and thus provides a stable supply of ACP for conversion to the acyl-ACP ligand required for repression by FabT. Indeed, and strains have essentially the same fatty acid synthesis phenotype in oleic acid-grown cultures, which argues that neither strain can form the FabT-acyl-ACP repression complex. Finally, acylated derivatives of both AcpB and AcpA were substrates for the enoyl-ACP reductases and for PlsX (acyl-ACP; phosphate acyltransferase). AcpB homologs are encoded by many, but not all, lactic acid bacteria (), including many members of the human microbiome. The mechanisms regulating fatty acid synthesis by exogenous fatty acids play a key role in resistance of these bacteria to those antimicrobials targeted at fatty acid synthesis enzymes. Defective regulation can increase resistance to such inhibitors and also reduce pathogenesis.
酰基载体蛋白（ACP）在脂肪酸的合成和长链脂肪酸酰基转移到复合脂质中发挥着重要作用。该 基因组包含两个注释的 基因，分别称为 和 AcpA 编码在脂肪酸合成（fab）操纵子内，似乎是必需的。相比之下，AcpB 是一种非典型的 ACP，与 AcpA 的残基同一性只有 30%，不是必需的。在缺乏脂肪酸的培养基中， 缺失对 生长或 脂肪酸合成没有影响。然而，与野生型菌株不同，在油酸生长的情况下， 脂肪酸合成几乎完全受阻，而 菌株在这些条件下仍能继续进行 脂肪酸合成。在野生型菌株中，这种阻断是由于 操纵子转录的抑制，导致脂肪酸合成蛋白（包括 AcpA）的水平不足以支持 合成。 操纵子的转录受 FabT 调节，FabT 是一种只有与酰基-ACP 配体结合时才结合 DNA 的阻遏蛋白。由于 AcpA 编码在 操纵子中，当操纵子被抑制时，其合成被阻断，因此不能为 FabT 结合 DNA 所需的酰基-ACP 配体的合成提供稳定的 ACP 供应。与 AcpA 不同， 转录不受外源性脂肪酸生长的影响，因此为 FabT 抑制所需的 ACP 转化为酰基-ACP 配体提供了稳定的供应。事实上， 和 菌株在油酸生长的培养物中具有基本相同的 脂肪酸合成表型，这表明这两种菌株都不能形成 FabT-酰基-ACP 抑制复合物。最后，AcpB 和 AcpA 的酰化衍生物都是烯酰-ACP 还原酶和 PlsX（酰基-ACP；磷酸酰基转移酶）的底物。AcpB 同源物由许多，但不是所有，乳杆菌（）编码，包括人类微生物组的许多成员。调节外源性脂肪酸对脂肪酸合成的作用对于这些细菌对抗那些针对脂肪酸合成酶的抗生素的抗性起着关键作用。调节缺陷会增加对这些抑制剂的抗性，也会降低发病机制。
