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Science 327 (5968): 1004-1007

Copyright © 2010 by the American Association for the Advancement of Science

Acetylation of Metabolic Enzymes Coordinates Carbon Source Utilization and Metabolic Flux

Qijun Wang,1 Yakun Zhang,2 Chen Yang,3 Hui Xiong,1,2 Yan Lin,4 Jun Yao,4 Hong Li,3 Lu Xie,3 Wei Zhao,3 Yufeng Yao,5 Zhi-Bin Ning,3 Rong Zeng,3 Yue Xiong,4,6 Kun-Liang Guan,4,7 Shimin Zhao,1,4,* Guo-Ping Zhao1,2,3,8,*

Abstract: Lysine acetylation regulates many eukaryotic cellular processes, but its function in prokaryotes is largely unknown. We demonstrated that central metabolism enzymes in Salmonella were acetylated extensively and differentially in response to different carbon sources, concomitantly with changes in cell growth and metabolic flux. The relative activities of key enzymes controlling the direction of glycolysis versus gluconeogenesis and the branching between citrate cycle and glyoxylate bypass were all regulated by acetylation. This modulation is mainly controlled by a pair of lysine acetyltransferase and deacetylase, whose expressions are coordinated with growth status. Reversible acetylation of metabolic enzymes ensure that cells respond environmental changes via promptly sensing cellular energy status and flexibly altering reaction rates or directions. It represents a metabolic regulatory mechanism conserved from bacteria to mammals.

1 State Key Laboratory of Genetic Engineering, Department of Microbiology, School of Life Sciences and Institute of Biomedical Sciences, Fudan University, Shanghai 200032, China.
2 MOST-Shanghai Laboratory of Disease and Health Genomics, Chinese National Human Genome Center at Shanghai, Shanghai 201203, China.
3 Key Laboratory of Synthetic Biology, Bioinformatics Center and Laboratory of Systems Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200032, China.
4 Molecular Cell Biology Laboratory, Institute of Biomedical Sciences, Fudan University, Shanghai 200032, China.
5 Laboratory of Human Bacterial Pathogenesis, Department of Medical Microbiology and Parasitology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
6 Department of Biochemistry and Biophysics and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
7 Department of Pharmacology and Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA.
8 Department of Microbiology and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China.

* To whom correspondence should be addressed. E-mail: zhaosm{at}fudan.edu.cn (S.Z.); gpzhao{at}sibs.ac.cn (G.-P.Z.)


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