Chemoproteomic profiling of itaconations in Salmonella |
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| Authors: | Yanling Zhang Wei Qin Dongyang Liu Yuan Liu Chu Wang |
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| Institution: | Synthetic and Functional Biomolecules Center, Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, China ; College of Chemistry and Molecular Engineering, China ; Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871 China, |
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| Abstract: | Itaconate is an immunoregulatory and anti-bacterial metabolite, and plays important roles in host–pathogen interactions. Chemoproteomic strategies have been used to explore the anti-inflammatory effects of itaconate on activated macrophages and it has been found that many key proteins in immune pathways were modified; however, how itaconate modulates pathogens was not fully understood. Here, we have designed and synthesized a series of itaconate-based bioorthogonal probes, which enable quantitative and site-specific profiling of itaconated proteins and sites in Salmonella. Among many proteins related to energy metabolism, we identified a key enzyme involved in the glyoxylate cycle, isocitrate lyase (ICL), as the most prominent target. Covalent modification of the active-site cysteine in ICL by itaconate abolishes the enzyme activity and suppresses bacterial growth. Our chemoproteomic study has uncovered the wide array of itaconation targets in Salmonella and provided a comprehensive resource for understanding the anti-bacterial function of this intriguing metabolite.Bioorthogonal probes have been developed to enable quantitative and site-specific profiling of itaconate modifications in Salmonella. |
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