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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} (S.Z.); gpzhao{at} (G.-P.Z.)

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H. A. Crosby and J. C. Escalante-Semerena (2014)
J. Bacteriol. 196, 1496-1504
   Abstract »    Full Text »    PDF »
Cross-talk between phosphorylation and lysine acetylation in a genome-reduced bacterium.
V. van Noort, J. Seebacher, S. Bader, S. Mohammed, I. Vonkova, M. J. Betts, S. Kuhner, R. Kumar, T. Maier, M. O'Flaherty, et al. (2014)
Mol Syst Biol 8, 571
   Abstract »    Full Text »    PDF »
Erasers of Histone Acetylation: The Histone Deacetylase Enzymes.
E. Seto and M. Yoshida (2014)
Cold Spring Harb Perspect Biol 6, a018713
   Abstract »    Full Text »    PDF »
Evolution and functional cross-talk of protein post-translational modifications.
P. Beltrao, P. Bork, N. J. Krogan, and V. van Noort (2014)
Mol Syst Biol 9, 714
   Abstract »    Full Text »    PDF »
Transcriptional regulation is insufficient to explain substrate-induced flux changes in Bacillus subtilis.
V. Chubukov, M. Uhr, L. Le Chat, R. J. Kleijn, M. Jules, H. Link, S. Aymerich, J. Stelling, and U. Sauer (2014)
Mol Syst Biol 9, 709
   Abstract »    Full Text »    PDF »
Acetylation control of metabolic enzymes in cancer: an updated version.
W. Huang, Z. Wang, and Q.-Y. Lei (2014)
Acta Biochim Biophys Sin 46, 204-213
   Abstract »    Full Text »    PDF »
Mitochondrial protein acetylation is driven by acetyl-CoA from fatty acid oxidation.
O. Pougovkina, H. te Brinke, R. Ofman, A. G. van Cruchten, W. Kulik, R. J. A. Wanders, S. M. Houten, and V. C. J. de Boer (2014)
Hum. Mol. Genet.
   Abstract »    Full Text »    PDF »
A new link between diabetes and cancer: enhanced WNT/{beta}-catenin signaling by high glucose.
C. Garcia-Jimenez, J. M. Garcia-Martinez, A. Chocarro-Calvo, and A. De la Vieja (2014)
J. Mol. Endocrinol. 52, R51-R66
   Abstract »    Full Text »    PDF »
Actinobacterial Acyl Coenzyme A Synthetases Involved in Steroid Side-Chain Catabolism.
I. Casabon, K. Swain, A. M. Crowe, L. D. Eltis, and W. W. Mohn (2014)
J. Bacteriol. 196, 579-587
   Abstract »    Full Text »    PDF »
Aldose Reductase Drives Hyperacetylation of Egr-1 in Hyperglycemia and Consequent Upregulation of Proinflammatory and Prothrombotic Signals.
S. Vedantham, D. Thiagarajan, R. Ananthakrishnan, L. Wang, R. Rosario, Y. S. Zou, I. Goldberg, S. F. Yan, A. M. Schmidt, and R. Ramasamy (2014)
Diabetes 63, 761-774
   Abstract »    Full Text »    PDF »
CPLM: a database of protein lysine modifications.
Z. Liu, Y. Wang, T. Gao, Z. Pan, H. Cheng, Q. Yang, Z. Cheng, A. Guo, J. Ren, and Y. Xue (2014)
Nucleic Acids Res. 42, D531-D536
   Abstract »    Full Text »    PDF »
Nitrogen Assimilation in Escherichia coli: Putting Molecular Data into a Systems Perspective.
W. C. van Heeswijk, H. V. Westerhoff, and F. C. Boogerd (2013)
Microbiol. Mol. Biol. Rev. 77, 628-695
   Abstract »    Full Text »    PDF »
Identification of Lysine Succinylation Substrates and the Succinylation Regulatory Enzyme CobB in Escherichia coli.
G. Colak, Z. Xie, A. Y. Zhu, L. Dai, Z. Lu, Y. Zhang, X. Wan, Y. Chen, Y. H. Cha, H. Lin, et al. (2013)
Mol. Cell. Proteomics 12, 3509-3520
   Abstract »    Full Text »    PDF »
Sirtuin 3 (SIRT3) Protein Regulates Long-chain Acyl-CoA Dehydrogenase by Deacetylating Conserved Lysines Near the Active Site.
S. S. Bharathi, Y. Zhang, A.-W. Mohsen, R. Uppala, M. Balasubramani, E. Schreiber, G. Uechi, M. E. Beck, M. J. Rardin, J. Vockley, et al. (2013)
J. Biol. Chem. 288, 33837-33847
   Abstract »    Full Text »    PDF »
Fueling Immunity: Insights into Metabolism and Lymphocyte Function.
E. L. Pearce, M. C. Poffenberger, C.-H. Chang, and R. G. Jones (2013)
Science 342, 1242454
   Abstract »    Full Text »    PDF »
Widespread and Enzyme-independent N{epsilon}-Acetylation and N{epsilon}-Succinylation of Proteins in the Chemical Conditions of the Mitochondrial Matrix.
G. R. Wagner and R. M. Payne (2013)
J. Biol. Chem. 288, 29036-29045
   Abstract »    Full Text »    PDF »
Acetylation of the Response Regulator RcsB Controls Transcription from a Small RNA Promoter.
L. I. Hu, B. K. Chi, M. L. Kuhn, E. V. Filippova, A. J. Walker-Peddakotla, K. Basell, D. Becher, W. F. Anderson, H. Antelmann, and A. J. Wolfe (2013)
J. Bacteriol. 195, 4174-4186
   Abstract »    Full Text »    PDF »
Reversible acetylation regulates acetate and propionate metabolism in Mycobacterium smegmatis.
J. D. Hayden, L. R. Brown, H. P. Gunawardena, E. F. Perkowski, X. Chen, and M. Braunstein (2013)
Microbiology 159, 1986-1999
   Abstract »    Full Text »    PDF »
Metabolic energy sensors (AMPK and SIRT1), protein carbonylation and cardiac failure as biomarkers of thermal stress in an intertidal limpet: linking energetic allocation with environmental temperature during aerial emersion.
G.-d. Han, S. Zhang, D. J. Marshall, C.-h. Ke, and Y.-w. Dong (2013)
J. Exp. Biol. 216, 3273-3282
   Abstract »    Full Text »    PDF »
Mitochondrial Sirtuins as Therapeutic Targets for Age-Related Disorders.
J. Shih and G. Donmez (2013)
Genes & Cancer
   Abstract »    Full Text »    PDF »
Mice Lacking {alpha}-Tubulin Acetyltransferase 1 Are Viable but Display {alpha}-Tubulin Acetylation Deficiency and Dentate Gyrus Distortion.
G.-W. Kim, L. Li, M. Gorbani, L. You, and X.-J. Yang (2013)
J. Biol. Chem. 288, 20334-20350
   Abstract »    Full Text »    PDF »
Inactivation of the Pta-AckA Pathway Causes Cell Death in Staphylococcus aureus.
M. R. Sadykov, V. C. Thomas, D. D. Marshall, C. J. Wenstrom, D. E. Moormeier, T. J. Widhelm, A. S. Nuxoll, R. Powers, and K. W. Bayles (2013)
J. Bacteriol. 195, 3035-3044
   Abstract »    Full Text »    PDF »
mChIP-KAT-MS, a method to map protein interactions and acetylation sites for lysine acetyltransferases.
L. Mitchell, S. Huard, M. Cotrut, R. Pourhanifeh-Lemeri, A.-L. Steunou, A. Hamza, J.-P. Lambert, H. Zhou, Z. Ning, A. Basu, et al. (2013)
PNAS 110, E1641-E1650
   Abstract »    Full Text »    PDF »
Abstract 2941: The role of lysine acetylation in the tumor cell response to stress..
L. Heppler and J. L. Andersen (2013)
Cancer Res. 73, 2941
Linking Post-Translational Modifications and Variation of Phenotypic Traits.
W. Albertin, P. Marullo, M. Bely, M. Aigle, A. Bourgais, O. Langella, T. Balliau, D. Chevret, B. Valot, T. da Silva, et al. (2013)
Mol. Cell. Proteomics 12, 720-735
   Abstract »    Full Text »    PDF »
Dephosphorylation at a Conserved SP Motif Governs cAMP Sensitivity and Nuclear Localization of Class IIa Histone Deacetylases.
D. R. Walkinshaw, R. Weist, L. Xiao, K. Yan, G.-W. Kim, and X.-J. Yang (2013)
J. Biol. Chem. 288, 5591-5605
   Abstract »    Full Text »    PDF »
SIRT3 Weighs Heavily in the Metabolic Balance: A New Role for SIRT3 in Metabolic Syndrome.
M. F. Green and M. D. Hirschey (2013)
J Gerontol A Biol Sci Med Sci 68, 105-107
   Abstract »    Full Text »    PDF »
Type III secretion system expression in oxygen-limited Pseudomonas aeruginosa cultures is stimulated by isocitrate lyase activity.
J. C. S. Chung, O. Rzhepishevska, M. Ramstedt, and M. Welch (2013)
Open Bio 3, 120131
   Abstract »    Full Text »    PDF »
Mitochondrial Protein Acylation and Intermediary Metabolism: Regulation by Sirtuins and Implications for Metabolic Disease.
J. C. Newman, W. He, and E. Verdin (2012)
J. Biol. Chem. 287, 42436-42443
   Abstract »    Full Text »    PDF »
Post-translational Modification of Serine/Threonine Kinase LKB1 via Adduction of the Reactive Lipid Species 4-Hydroxy-trans-2-nonenal (HNE) at Lysine Residue 97 Directly Inhibits Kinase Activity.
T. D. Calamaras, C. Lee, F. Lan, Y. Ido, D. A. Siwik, and W. S. Colucci (2012)
J. Biol. Chem. 287, 42400-42406
   Abstract »    Full Text »    PDF »
Structural Insights into the Substrate Specificity of the Rhodopseudomonas palustris Protein Acetyltransferase RpPat: IDENTIFICATION OF A LOOP CRITICAL FOR RECOGNITION BY RpPat.
H. A. Crosby, K. C. Rank, I. Rayment, and J. C. Escalante-Semerena (2012)
J. Biol. Chem. 287, 41392-41404
   Abstract »    Full Text »    PDF »
Environmental Proteomics of the Mussel Mytilus: Implications for Tolerance to Stress and Change in Limits of Biogeographic Ranges in Response to Climate Change.
L. Tomanek (2012)
Integr. Comp. Biol. 52, 648-664
   Abstract »    Full Text »    PDF »
Proteome-wide Analysis of Lysine Acetylation Suggests its Broad Regulatory Scope in Saccharomyces cerevisiae.
P. Henriksen, S. A. Wagner, B. T. Weinert, S. Sharma, G. Bacinskaja, M. Rehman, A. H. Juffer, T. C. Walther, M. Lisby, and C. Choudhary (2012)
Mol. Cell. Proteomics 11, 1510-1522
   Abstract »    Full Text »    PDF »
Genetic basis of kidney cancer: Role of genomics for the development of disease-based therapeutics.
W. M. Linehan (2012)
Genome Res. 22, 2089-2100
   Abstract »    Full Text »    PDF »
Autoacetylation of the MYST Lysine Acetyltransferase MOF Protein.
C. Yang, J. Wu, S. H. Sinha, J. M. Neveu, and Y. G. Zheng (2012)
J. Biol. Chem. 287, 34917-34926
   Abstract »    Full Text »    PDF »
Structural and mechanistic insights into the bifunctional enzyme isocitrate dehydrogenase kinase/phosphatase AceK.
J. Zheng, S. P. Yates, and Z. Jia (2012)
Phil Trans R Soc B 367, 2656-2668
   Abstract »    Full Text »    PDF »
Acetylation of malate dehydrogenase 1 promotes adipogenic differentiation via activating its enzymatic activity.
E. Y. Kim, W. K. Kim, H. J. Kang, J.-H. Kim, S. J. Chung, Y. S. Seo, S. G. Park, S. C. Lee, and K.-H. Bae (2012)
J. Lipid Res. 53, 1864-1876
   Abstract »    Full Text »    PDF »
Fueling the flame: bioenergy couples metabolism and inflammation.
T. F. Liu, C. M. Brown, M. El Gazzar, L. McPhail, P. Millet, A. Rao, V. T. Vachharajani, B. K. Yoza, and C. E. McCall (2012)
J. Leukoc. Biol. 92, 499-507
   Abstract »    Full Text »    PDF »
NAD+/NADH and skeletal muscle mitochondrial adaptations to exercise.
A. T. White and S. Schenk (2012)
Am J Physiol Endocrinol Metab 303, E308-E321
   Abstract »    Full Text »    PDF »
Lysine Acetylation Is Widespread on Proteins of Diverse Function and Localization in the Protozoan Parasite Toxoplasma gondii.
V. Jeffers and W. J. Sullivan Jr. (2012)
Eukaryot. Cell 11, 735-742
   Abstract »    Full Text »    PDF »
More than a store: regulatory roles for glycogen in skeletal muscle adaptation to exercise.
A. Philp, M. Hargreaves, and K. Baar (2012)
Am J Physiol Endocrinol Metab 302, E1343-E1351
   Abstract »    Full Text »    PDF »
System-wide Studies of N-Lysine Acetylation in Rhodopseudomonas palustris Reveal Substrate Specificity of Protein Acetyltransferases.
H. A. Crosby, D. A. Pelletier, G. B. Hurst, and J. C. Escalante-Semerena (2012)
J. Biol. Chem. 287, 15590-15601
   Abstract »    Full Text »    PDF »
Function and Molecular Mechanism of Acetylation in Autophagy Regulation.
C. Yi, M. Ma, L. Ran, J. Zheng, J. Tong, J. Zhu, C. Ma, Y. Sun, S. Zhang, W. Feng, et al. (2012)
Science 336, 474-477
   Abstract »    Full Text »    PDF »
MYST protein acetyltransferase activity requires active site lysine autoacetylation.
H. Yuan, D. Rossetto, H. Mellert, W. Dang, M. Srinivasan, J. Johnson, S. Hodawadekar, E. C. Ding, K. Speicher, N. Abshiru, et al. (2012)
EMBO J. 31, 58-70
   Abstract »    Full Text »    PDF »
Post-translational modification of RNase R is regulated by stress-dependent reduction in the acetylating enzyme Pka (YfiQ).
W. Liang and M. P. Deutscher (2012)
RNA 18, 37-41
   Abstract »    Full Text »    PDF »
Panhistone deacetylase inhibitors inhibit proinflammatory signaling pathways to ameliorate interleukin-18-induced cardiac hypertrophy.
G. Majumdar, R. J. Rooney, I. M. Johnson, and R. Raghow (2011)
Physiol Genomics 43, 1319-1333
   Abstract »    Full Text »    PDF »
Sirt5 Is a NAD-Dependent Protein Lysine Demalonylase and Desuccinylase.
J. Du, Y. Zhou, X. Su, J. J. Yu, S. Khan, H. Jiang, J. Kim, J. Woo, J. H. Kim, B. H. Choi, et al. (2011)
Science 334, 806-809
   Abstract »    Full Text »    PDF »
Purification and characterization of the acetyl-CoA synthetase from Mycobacterium tuberculosis.
R. Li, J. Gu, P. Chen, Z. Zhang, J. Deng, and X. Zhang (2011)
Acta Biochim Biophys Sin 43, 891-899
   Abstract »    Full Text »    PDF »
Biochemical and Thermodynamic Analyses of Salmonella enterica Pat, a Multidomain, Multimeric N{varepsilon}-Lysine Acetyltransferase Involved in Carbon and Energy Metabolism.
S. Thao and J. C. Escalante-Semerena (2011)
mBio 2, e00216-11
   Abstract »    Full Text »    PDF »
Metabolic signals regulate SIRT1 expression.
A. Chalkiadaki and L. Guarente (2011)
EMBO Rep. 12, 985-986
   Full Text »    PDF »
Sirtuin 1 (SIRT1) Deacetylase Activity Is Not Required for Mitochondrial Biogenesis or Peroxisome Proliferator-activated Receptor-{gamma} Coactivator-1{alpha} (PGC-1{alpha}) Deacetylation following Endurance Exercise.
A. Philp, A. Chen, D. Lan, G. A. Meyer, A. N. Murphy, A. E. Knapp, I. M. Olfert, C. E. McCurdy, G. R. Marcotte, M. C. Hogan, et al. (2011)
J. Biol. Chem. 286, 30561-30570
   Abstract »    Full Text »    PDF »
Functional Analyses of Two Acetyl Coenzyme A Synthetases in the Ascomycete Gibberella zeae.
S. Lee, H. Son, J. Lee, K. Min, G. J. Choi, J.-C. Kim, and Y.-W. Lee (2011)
Eukaryot. Cell 10, 1043-1052
   Abstract »    Full Text »    PDF »
Proteome-Wide Mapping of the Drosophila Acetylome Demonstrates a High Degree of Conservation of Lysine Acetylation.
B. T. Weinert, S. A. Wagner, H. Horn, P. Henriksen, W. R. Liu, J. V. Olsen, L. J. Jensen, and C. Choudhary (2011)
Science Signaling 4, ra48
   Abstract »    Full Text »    PDF »
Increased Acetylation in the DNA-binding Domain of TR4 Nuclear Receptor by the Coregulator ARA55 Leads to Suppression of TR4 Transactivation.
S. Xie, J. Ni, Y.-F. Lee, S. Liu, G. Li, C.-R. Shyr, and C. Chang (2011)
J. Biol. Chem. 286, 21129-21136
   Abstract »    Full Text »    PDF »
Proteins of Diverse Function and Subcellular Location Are Lysine Acetylated in Arabidopsis.
I. Finkemeier, M. Laxa, L. Miguet, A. J. M. Howden, and L. J. Sweetlove (2011)
Plant Physiology 155, 1779-1790
   Abstract »    Full Text »    PDF »
Lysine Acetylation Is a Widespread Protein Modification for Diverse Proteins in Arabidopsis.
X. Wu, M.-H. Oh, E. M. Schwarz, C. T. Larue, M. Sivaguru, B. S. Imai, P. M. Yau, D. R. Ort, and S. C. Huber (2011)
Plant Physiology 155, 1769-1778
   Abstract »    Full Text »    PDF »
Sirtuins, Aging, and Metabolism.
L. Guarente (2011)
Cold Spring Harb Symp Quant Biol 76, 81-90
   Abstract »    Full Text »    PDF »
SIRT3 Regulates Mitochondrial Protein Acetylation and Intermediary Metabolism.
M. D. Hirschey, T. Shimazu, J.- Y. Huang, B. Schwer, and E. Verdin (2011)
Cold Spring Harb Symp Quant Biol 76, 267-277
   Abstract »    Full Text »    PDF »
On Acetyl-CoA as a Gauge of Cellular Metabolic State.
L. Cai and B. P. Tu (2011)
Cold Spring Harb Symp Quant Biol 76, 195-202
   Abstract »    Full Text »    PDF »
Back to the Future: Molecular Biology Meets Metabolism.
S. L. McKnight (2011)
Cold Spring Harb Symp Quant Biol 76, 403-411
   Full Text »    PDF »
Regulation of Glycolysis and Gluconeogenesis by Acetylation of PKM and PEPCK.
Y. Xiong, Q.-Y. Lei, S. Zhao, and K.-L. Guan (2011)
Cold Spring Harb Symp Quant Biol 76, 285-289
   Abstract »    Full Text »    PDF »
CPLA 1.0: an integrated database of protein lysine acetylation.
Z. Liu, J. Cao, X. Gao, Y. Zhou, L. Wen, X. Yang, X. Yao, J. Ren, and Y. Xue (2011)
Nucleic Acids Res. 39, D1029-D1034
   Abstract »    Full Text »    PDF »
The hexosamine biosynthetic pathway couples growth factor-induced glutamine uptake to glucose metabolism.
K. E. Wellen, C. Lu, A. Mancuso, J. M. S. Lemons, M. Ryczko, J. W. Dennis, J. D. Rabinowitz, H. A. Coller, and C. B. Thompson (2010)
Genes & Dev. 24, 2784-2799
   Abstract »    Full Text »    PDF »
Biologically Active Isoforms of CobB Sirtuin Deacetylase in Salmonella enterica and Erwinia amylovora.
A. C. Tucker and J. C. Escalante-Semerena (2010)
J. Bacteriol. 192, 6200-6208
   Abstract »    Full Text »    PDF »
The proteomic response of the mussel congeners Mytilus galloprovincialis and M. trossulus to acute heat stress: implications for thermal tolerance limits and metabolic costs of thermal stress.
L. Tomanek and M. J. Zuzow (2010)
J. Exp. Biol. 213, 3559-3574
   Abstract »    Full Text »    PDF »
Mass spectrometry-based proteomics in cell biology.
T. C. Walther and M. Mann (2010)
J. Cell Biol. 190, 491-500
   Abstract »    Full Text »    PDF »
cAMP-regulated Protein Lysine Acetylases in Mycobacteria.
S. Nambi, N. Basu, and S. S. Visweswariah (2010)
J. Biol. Chem. 285, 24313-24323
   Abstract »    Full Text »    PDF »
ATP-Citrate Lyase Is Required for Production of Cytosolic Acetyl Coenzyme A and Development in Aspergillus nidulans.
M. J. Hynes and S. L. Murray (2010)
Eukaryot. Cell 9, 1039-1048
   Abstract »    Full Text »    PDF »
Rise of the Rival.
A. Norvell and S. B. McMahon (2010)
Science 327, 964-965
   Abstract »    Full Text »    PDF »

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