Modulation of Central Carbon Metabolism by Acetylation of Isocitrate Lyase in Mycobacterium tuberculosis.
Several enzymes involved in central carbon metabolism such as isocitrate lyase and phosphoenolpyruvate carboxykinase are key determinants of pathogenesis of Mycobacterium tuberculosis (M. tb). In this study, we found that lysine acetylation plays an important role in the modulation of central carbon metabolism in M. tb. Mutant of M. tb defective in sirtuin deacetylase exhibited improved growth in fatty acid-containing media. Global analysis of lysine acetylome of M. tb identified three acetylated lysine residues (K322, K331, and K392) of isocitrate lyase (ICL1). Using a genetically encoding system, we demonstrated that acetylation of K392 increased the enzyme activity of ICL1, whereas acetylation of K322 decreased its activity. Antibodies that specifically recognized acetyllysine at 392 and 322 of ICL1 were used to monitor the levels of ICL1 acetylation in M. tb cultures. The physiological significance of ICL1 acetylation was demonstrated by the observation that M. tb altered the levels of acetylated K392 in response to changes of carbon sources, and that acetylation of K392 affected the abundance of ICL1 protein. Our study has uncovered another regulatory mechanism of ICL1.
State Key Laboratory of Genetic Engineering, School of Life Science, Fudan University, Shanghai, China.
Jing
J
Bi
State Key Laboratory of Genetic Engineering, School of Life Science, Fudan University, Shanghai, China.
Yihong
Y
Wang
NPFPC Key Laboratory of Contraceptives and Devices, Shanghai Institute of Planned Parenthood Research, Institutes of Reproduction and Development, Shanghai, China.
Heguo
H
Yu
State Key Laboratory of Genetic Engineering, School of Life Science, Fudan University, Shanghai, China.
Xiaoyan
X
Qian
State Key Laboratory of Genetic Engineering, School of Life Science, Fudan University, Shanghai, China.
Honghai
H
Wang
State Key Laboratory of Genetic Engineering, School of Life Science, Fudan University, Shanghai, China.|Department of Molecular Genetics, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Jun
J
Liu
State Key Laboratory of Genetic Engineering, School of Life Science, Fudan University, Shanghai, China.
Xuelian
X
Zhang
D000107:Acetylation; D002244:Carbon / Q000378:metabolism*; D004734:Energy Metabolism; D005227:Fatty Acids; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism; D007522:Isocitrate Lyase / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D010641:Phenotype; D014158:Transcription, Genetic
D005227:Fatty Acids; D002244:Carbon; D007522:Isocitrate Lyase; D008239:Lysine