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ORIGINAL RESEARCH article

Front. Microbiol.
Sec. Microbial Physiology and Metabolism
Volume 15 - 2024 | doi: 10.3389/fmicb.2024.1503184
This article is part of the Research Topic Advancements in Proteomics and PTMomics: Unveiling Mechanistic Insights and Targeted Therapies for Metabolic Diseases View all 4 articles

Characterization of Acidic Lysine Acylations in Mycobacteria

Provisionally accepted
Junyu Xu Junyu Xu 1*Tong Ye Tong Ye 2Danfeng Wang Danfeng Wang 3Yewen Sun Yewen Sun 4Shuyu Xie Shuyu Xie 2Tianqi Liu Tianqi Liu 4Nana Tian Nana Tian 3Minjia Tan Minjia Tan 1
  • 1 Shanghai Institute of Materia Medica, Chinese Academy of Sciences (CAS), Shanghai, China
  • 2 Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China
  • 3 Zunyi Medical University, Zunyi, Guizhou Province, China
  • 4 Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences (CAS), Zhongshan, China

The final, formatted version of the article will be published soon.

    Protein acetylation is an extensively investigated post-translational modification (PTM) that exerts regulatory role in a diverse array of biological processes in both eukaryotic and prokaryotic organisms. In addition to lysine acetylation, three new types of lysine acylations characterized by the presence of an acidic carboxylic group have been recently identified and validated through mass spectrometry. These included lysine malonylation (Kmal), lysine succinylation (Ksucc) and lysine glutarylation (Kglu). Pathogens belonging to the genus Mycobacterium elicit severe diseases in mammalian hosts through the modulation of energy metabolism pathways. Throughout this process, malonyl-CoA, succinyl-CoA and glutaryl-CoA are important intermediates in metabolic pathways, including the tricarboxylic acid (TCA) cycle, amino acid and lipid metabolism. These short-chain acyl-CoAs serve as substrates for corresponding acidic lysine acylation reactions. Here, we systematically investigated the global substrate characterization of 1,703 lysine malonylated sites, 5,320 lysine succinylated sites and 269 lysine glutarylated sites in the non-pathogenic model strain Mycobacterium smegmatis. Bioinformatics analysis demonstrated a correlation between these acidic lysine acylations and the functional roles of ribosomes, in addition to their roles in various metabolic pathways. Furthermore, we investigated the impact of lysine acylations on the functional activity of adenylate kinase and proteasome-associated ATPase, as well as their roles in mycobacterial infection process. Collectively, our study provided an important resource on substrate characterization and functional regulation of acidic lysine acylations in Mycobacterium smegmatis, giving valuable insights into their interrelation with the biology of infectious process.

    Keywords: Mycobacterium smegmatis, acidic lysine acylation, lysine malonylation, lysine succinylation, lysine glutarylation, Functional regulation

    Received: 30 Sep 2024; Accepted: 27 Nov 2024.

    Copyright: © 2024 Xu, Ye, Wang, Sun, Xie, Liu, Tian and Tan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Junyu Xu, Shanghai Institute of Materia Medica, Chinese Academy of Sciences (CAS), Shanghai, China

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