Sc CobB2-mediated Lysine Desuccinylation Regulates Protein Biosynthesis and Carbon Metabolism in Streptomyces coelicolor

• Published in: Molecular & cellular proteomics 2019-10, Vol.18 (10), p.2003
• Main Authors: Zhang, Hong, Li, Peng, Ren, Shuangxi, Cheng, Zhongyi, Zhao, Guoping, Zhao, Wei
• Format: Article
• Language: English
• Subjects: Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Carbon - metabolism; Chromatography, Liquid; Gene Expression Regulation, Bacterial; Gene Knockout Techniques; Lysine - metabolism; Protein Biosynthesis; Protein Processing, Post-Translational; Proteomics - methods; Sirtuins - genetics; Sirtuins - metabolism; Soil Microbiology; Streptomyces coelicolor - genetics; Streptomyces coelicolor - metabolism; Succinates - metabolism; Tandem Mass Spectrometry
• ISSN: 1535-9484
• DOI: 10.1074/mcp.RA118.001298

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 , we biochemically characterized a sirtuin-like protein CobB2 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 Δ to the wild-type succinylome 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 Δ cells. We experimentally examined the regulatory roles of CobB2 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 , laying the foundation for future research of succinylation regulation in other microorganisms.