Global Profiling of Protein Lysine Malonylation in Escherichia coli Reveals Its Role in Energy Metabolism

Author

Lili Qian^†‡, Litong Nie^†‡, Ming Chen^†‡, Ping Liu^†‡, Jun Zhu^#, Linhui Zhai^†‡, Sheng-ce Tao^⊥, Zhongyi Cheng^#, Yingming Zhao^†‡§ and Minjia Tan^*†‡

*Tel.: 86-21-50800172. Fax: 86-21-50800172. E-mail: mjtan@simm.ac.cn.

†The Chemical Proteomics Center and State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China

‡University of Chinese Academy of Sciences, Beijing 100049, PR China

#Jingjie PTM BioLab (Hangzhou) Co. Ltd, Hangzhou 310018, PR China

⊥Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, PR China

§Ben May Department for Cancer Research, University of Chicago, Chicago, Illinois 60637, United States

Journal of Proteome Research

Vol. 15: Issue. 6: Pages. 2060-2071

Publication Date (Web): May 16, 2016

DOI: 10.1021/acs.jproteome.6b00264

Protein lysine malonylation is a recently identified post-translational modification (PTM), which is evolutionarily conserved from bacteria to mammals. Although analysis of lysine malonylome in mammalians suggested that this modification was related to energy metabolism, the substrates and biological roles of malonylation in prokaryotes are still poorly understood. In this study, we performed qualitative and quantitative analyses to globally identify lysine malonylation substrates in Escherichia coli. We identified 1745 malonylation sites in 594 proteins in E. coli, representing the first and largest malonylome data set in prokaryotes up to date. Bioinformatic analyses showed that lysine malonylation was significantly enriched in protein translation, energy metabolism pathways and fatty acid biosynthesis, implying the potential roles of protein malonylation in bacterial physiology. Quantitative proteomics by fatty acid synthase inhibition in both auxotrophic and prototrophic E. coli strains revealed that lysine malonylation is closely associated with E. coli fatty acid metabolism. Protein structural analysis and mutagenesis experiment suggested malonylation could impact enzymatic activity of citrate synthase, a key enzyme in citric acid (TCA) cycle. Further comparative analysis among lysine malonylome, succinylome and acetylome data showed that these three modifications could participate in some similar enriched metabolism pathways, but they could also possibly play distinct roles such as in fatty acid synthesis. These data expanded our knowledge of lysine malonylation in prokaryotes, providing a resource for functional study of lysine malonylation in bacteria.

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http://pubs.acs.org/doi/abs/10.1021/acs.jproteome.6b00205#/doi/full/10.1021/acs.jproteome.6b00208