ScCobB2-mediated Lysine Desuccinylation Regulates Protein Biosynthesis and Carbon Metabolism in Streptomyces coelicolor[S]

• Published in: Molecular & cellular proteomics Vol. 18; no. 10; pp. 2003 - 2017
• Main Authors: Zhang, Hong, Li, Peng, Ren, Shuangxi, Cheng, Zhongyi, Zhao, Guoping, Zhao, Wei
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2019
• Subjects: Acetylation; Bacteria; Desuccinylase; Enzyme Modification; Evolution; Lysine Succinylation; Metabolites; Microbiology; Posttranslational Modification; Quantification; ScCobB2; Succinylome; Desuccinylase; Metabolites; Quantification; Microbiology; Lysine Succinylation; Enzyme Modification; Bacteria; Evolution; Acetylation; Posttranslational Modification; Succinylome; ScCobB2
• ISSN: 1535-9476; 1535-9484
• DOI: 10.1074/mcp.RA118.001298

Lysine succinylation is a prevalent protein modification that regulates multiple critical cellular processes. Here, we performed a quantitative succinylome analysis in the model soil bacterium Streptomyces coelicolor after characterization of a specific desuccinylase ScCobB2. Comparison of the ΔScCobB2 to the wild-type succinylome identified a total of 673 unique succinylated sites, and among which, 144 protein sites are statistically hypersuccinylated in ΔScCobB2 cells. Analyses of these hypersuccinylated proteins suggested they are enriched in two major pathways, protein biosynthesis and carbon metabolism. We propose that ScCobB2 has critical regulatory roles in S. coelicolor cellular physiology. [Display omitted] Highlights •Identification of the first evolutionary divergent sirtuin ScCobB2 in bacteria.•Implementing a global quantitative succinylome between ΔScCobB2 and WT cells.•ScCobB2 regulates S. coelicolor protein biosynthesis and carbon metabolism pathways.•The divergent sirtuin enzymes are prevalent in other groups of Actinobacteria. As a recently discovered protein posttranslational modification in eukaryotes, lysine succinylation has attracted increasing interest due to its ability to regulate several critical cellular processes, including catabolism, β-oxidation, and ketogenesis. Nevertheless, understanding of the regulatory mechanisms is still at an early stage due to the lack of identified specific desuccinylases in microorganisms. Here, in the model soil bacterium Streptomyces coelicolor, we biochemically characterized a sirtuin-like protein ScCobB2 as a divergent desuccinylase. Based on it, we were able to identify a total of 673 unique succinylated sites, of which 470 sites in 317 proteins were quantified by comparing the ΔScCobB2 to the wild-type succinylome via LC-MS/MS analysis. Further analyses of the quantitative succinylome revealed that at least 114 proteins representing two major pathways, protein biosynthesis and carbon metabolism, are obviously hypersuccinylated in ΔScCobB2 cells. We experimentally examined the regulatory roles of ScCobB2 on 13 hypersuccinylated proteins, including glyceraldehyde-3-phosphate dehydrogenase, aconitate hydratase, and several ribosomal proteins, the results of which suggested a high confidence in our quantitative data. This work provided the first discovery of a specific desuccinylase in bacteria and demonstrated it has pivotal regulatory roles in multiple biological processes of S. coelicolor, laying the foundation for future research of succinylation regulation in other microorganisms.