Lysine lactylation regulates metabolic pathways and biofilm formation in Streptococcus mutans

IF 6.7 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Science Signaling Pub Date : 2023-09-05 DOI:10.1126/scisignal.adg1849

Zhengyi Li, Tao Gong, Qinrui Wu, Yixin Zhang, Xin Zheng, Yuqing Li, Biao Ren, Xian Peng, Xuedong Zhou

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引用次数: 0

Abstract

In eukaryotes, lactate produced during glycolysis is involved in regulating multiple metabolic processes through lysine lactylation (Kla). To explore the potential link between metabolism and Kla in prokaryotes, we investigated the distribution of Kla in the cariogenic bacterium Streptococcus mutans during planktonic growth in low-sugar conditions and in biofilm-promoting, high-sugar conditions. We identified 1869 Kla sites in 469 proteins under these two conditions, with the biofilm growth state showing a greater number of lactylated sites and proteins. Although high sugar increased Kla globally, it reduced lactylation of RNA polymerase subunit α (RpoA) at Lys¹⁷³. Lactylation at this residue inhibited the synthesis of extracellular polysaccharides, a major constituent of the cariogenic biofilm. The Gcn5-related N-acetyltransferase (GNAT) superfamily enzyme GNAT13 exhibited lysine lactyltransferase activity in cells and lactylated Lys¹⁷³ in RpoA in vitro. Either GNAT13 overexpression or lactylation of Lys¹⁷³ in RpoA inhibited biofilm formation. These results provide an overview of the distribution and potential functions of Kla and improve our understanding of the role of lactate in the metabolic regulation of prokaryotes.

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赖氨酸乳化调节变异链球菌的代谢途径和生物膜的形成

在真核生物中，糖酵解过程中产生的乳酸通过赖氨酸乳酰化（Kla）参与调节多种代谢过程。为了探索原核生物中新陈代谢与 Kla 之间的潜在联系，我们研究了变异链球菌在低糖条件下浮游生长和高糖条件下生物膜促进生长过程中 Kla 的分布情况。在这两种条件下，我们在 469 个蛋白质中发现了 1869 个 Kla 位点，其中生物膜生长状态下的乳化位点和蛋白质数量更多。虽然高糖在全球范围内增加了 Kla，但却减少了 RNA 聚合酶亚基 α（RpoA）在 Lys173 处的乳化作用。该残基的乳化抑制了致龋生物膜的主要成分--细胞外多糖的合成。Gcn5 相关 N-乙酰转移酶（GNAT）超家族酶 GNAT13 在细胞中表现出赖氨酸乳酰转移酶活性，并在体外对 RpoA 的 Lys173 进行乳化。过表达 GNAT13 或对 RpoA 中的 Lys173 进行乳化均可抑制生物膜的形成。这些结果概述了 Kla 的分布和潜在功能，增进了我们对乳酸在原核生物代谢调节中的作用的了解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Science Signaling BIOCHEMISTRY & MOLECULAR BIOLOGY-CELL BIOLOGY

CiteScore

9.50

自引率

0.00%

发文量

148

审稿时长

3-8 weeks

期刊介绍： "Science Signaling" is a reputable, peer-reviewed journal dedicated to the exploration of cell communication mechanisms, offering a comprehensive view of the intricate processes that govern cellular regulation. This journal, published weekly online by the American Association for the Advancement of Science (AAAS), is a go-to resource for the latest research in cell signaling and its various facets. The journal's scope encompasses a broad range of topics, including the study of signaling networks, synthetic biology, systems biology, and the application of these findings in drug discovery. It also delves into the computational and modeling aspects of regulatory pathways, providing insights into how cells communicate and respond to their environment. In addition to publishing full-length articles that report on groundbreaking research, "Science Signaling" also features reviews that synthesize current knowledge in the field, focus articles that highlight specific areas of interest, and editor-written highlights that draw attention to particularly significant studies. This mix of content ensures that the journal serves as a valuable resource for both researchers and professionals looking to stay abreast of the latest advancements in cell communication science.