YiaC and CobB regulate lysine lactylation in Escherichia coli.

YiaC and CobB regulate lysine lactylation in Escherichia coli.
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YiaC 和 CobB 调节大肠杆菌中的赖氨酸乳酰化

DOI:
10.1038/s41467-022-34399-y
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发表时间:
2022-11-04
影响因子:
16.6
通讯作者:
Zhang, Kai
Zhang, Kai
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Dong, Hanyang;Zhang, Jianji;Zhang, Hui;Han, Yue;Lu, Congcong;Chen, Chen;Tan, Xiaoxia;Wang, Siyu;Bai, Xue;Zhai, Guijin;Tian, Shanshan;Zhang, Tao;Cheng, Zhongyi;Li, Enmin;Xu, Liyan;Zhang, Kai

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赖氨酸乳酸化(KLA)最近被报道参与调节人类细胞的转录。然而,KLA在原核生物中的特性、调控机制和功能结果仍不清楚。在此,我们报道了YaC作为赖氨酸乳糖酶的功能,以及CobB作为赖氨酸乳糖酶在代谢调节中的作用。我们证明,在体外和细胞内,YaC催化KLA的加成,而Cobb则消除这种PTM。此外,我们还发现YdiF可以催化形成乳酰辅酶A,为KLA提供乳酸基。定量蛋白质组学分析进一步揭示了在大肠杆菌中Cobb靶向的446个内源KLA位点和YAC靶向的79个候选者。此外,我们还发现KLA可以影响代谢酶的功能。有趣的是,我们证明了Cobb可以通过调节K382la,促进糖酵解和细菌生长来特异性地调节PykF的活性。我们的研究确定了KLA的调节酶和功能网络,并揭示了KLA介导的、由Cobb催化的调节大肠杆菌糖酵解的分子机制。
Lysine lactylation (Kla) has recently been reported to participate in regulating transcription in human cells. However, the characterization, regulatory mechanism and functional consequence of Kla in prokaryotes remain unclear. Here, we report that YiaC functions as a lysine lactylase and that CobB serves as a lysine delactylase in the regulation of metabolism. We demonstrate that YiaC catalyzes the addition of Kla, while CobB erases this PTM both in vitro and intracellularly. Moreover, we show that YdiF can catalyze the formation of a lactyl-coenzyme A, which donates lactyl group for Kla. Quantitative proteomic analysis further reveals 446 endogenous Kla sites targeted by CobB and 79 candidates targeted by YiaC in Escherichia coli (E. coli). Furthermore, we present that Kla can influence the functions of metabolic enzymes. Interestingly, we demonstrate that CobB can specifically modulate the activity of PykF by regulating K382la, promoting glycolysis and bacterial growth. Our study identifies the regulatory enzymes and functional network of Kla and reveals a Kla-mediated molecular mechanism catalyzed by CobB for glycolysis regulation in E. coli.
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