Department of Agricultural Biotechnology, Seoul National University, Seoul, 08826, Republic of Korea.
Sci Rep. 2019 Jul 30;9(1):11038. doi: 10.1038/s41598-019-47460-6.
The activated methyl cycle (AMC) is responsible for the generation of S-adenosylmethionine (SAM), which is a substrate of N-acylhomoserine lactone (AHL) synthases. However, it is unknown whether AHL-mediated quorum sensing (QS) plays a role in the metabolic flux of the AMC to ensure cell density-dependent biosynthesis of AHL in cooperative populations. Here we show that QS controls metabolic homeostasis of the AMC critical for AHL biosynthesis and cellular methylation in Burkholderia glumae, the causal agent of rice panicle blight. Activation of genes encoding SAM-dependent methyltransferases, S-adenosylhomocysteine (SAH) hydrolase, and methionine synthases involved in the AMC by QS is essential for maintaining the optimal concentrations of methionine, SAM, and SAH required for bacterial cooperativity as cell density increases. Thus, the absence of QS perturbed metabolic homeostasis of the AMC and caused pleiotropic phenotypes in B. glumae. A null mutation in the SAH hydrolase gene negatively affected AHL and ATP biosynthesis and the activity of SAM-dependent methyltransferases including ToxA, which is responsible for the biosynthesis of a key virulence factor toxoflavin in B. glumae. These results indicate that QS controls metabolic flux of the AMC to secure the biosynthesis of AHL and cellular methylation in a cooperative population.
激活甲基循环（AMC）负责生成 S-腺苷甲硫氨酸（SAM），SAM 是 N-酰基高丝氨酸内酯（AHL）合成酶的底物。然而，目前尚不清楚 AHL 介导的群体感应（QS）是否在 AMC 的代谢通量中起作用，以确保合作群体中 AHL 的细胞密度依赖性生物合成。在这里，我们表明 QS 控制了 AMC 的代谢稳态，这对于稻瘟病菌（引起稻穗枯病的病原体）中 AHL 生物合成和细胞甲基化至关重要。QS 激活编码 SAM 依赖性甲基转移酶、S-腺苷同型半胱氨酸（SAH）水解酶和参与 AMC 的甲硫氨酸合成酶的基因对于维持随着细胞密度增加所需的甲硫氨酸、SAM 和 SAH 的最佳浓度以实现细菌协同作用是必需的。因此，QS 的缺失破坏了 AMC 的代谢稳态，并导致稻瘟病菌出现多种表型。SAH 水解酶基因的缺失突变对 AHL 和 ATP 生物合成以及 SAM 依赖性甲基转移酶的活性产生负面影响，包括 ToxA，它负责稻瘟病菌中关键毒力因子 toxoflavin 的生物合成。这些结果表明，QS 控制 AMC 的代谢通量，以确保合作群体中 AHL 的生物合成和细胞甲基化。
