In nature, microbes face a spectacular array of stimuli that challenge their survival. Collectively, these stimuli exert a strong selective pressure for th evolution of sophisticated, rapid-response mechanisms that can efficiently maintain homeostasis through the modulation of functions of diverse biomolecules. Not surprisingly, biologists are interested in understanding how these mechanisms work, how they are regulated, and how they are integrated into the cellular regulatory circuits. The PI's laboratory studies the control of protein function by chemical modifications, with an emphasis on reversible lysine acylation (RLA). Ten years ago, the PI's group reported the first evidence of RLA in prokaryotes, a discovery that elicited a great deal of interest. In a short period of time, RLA has emerged as a posttranslational modification that rivals phosphorylation in terms of its breadth and impact on the dynamics of the complex metabolic network of the cell. In recent years, the PI's group has reported the impact of RLA on central cellular processes such as cell motility, gene expression, carbon metabolism, energy and coenzyme A homeostasis. The PI's laboratory studies the control of protein function by RLA. The long-term goal of the work supported by grant R01-GM062203 is to understand the contributions of RLA to cell function. The PI's group will continue to apply comprehensive genetic, molecular biological, biochemical, structural, and system-wide approaches to answer fundamental questions regarding the mechanism of RLA function. Work proposed herein seeks to: i) learn the molecular details of how acetyltransferases recognize their protein substrates;ii) gain insights into the mechanism of acetyltransferase function;iii) gain a better understanding of how proteins evolve to escape RLA control;and iv) define the regulatory circuit that integrates RLA into the complex metabolic network of the cell.

Public Health Relevance

Reversible lysine acetylation (RLA) is a regulatory mechanism for the control of protein function that offers unique opportunities for improving human health and biotechnology. Our understanding of how RLA works, how it is regulated and integrated into the metabolic network, is very limited. The proposed work will fill gaps of basic knowledge about the system in these areas.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
Project #
Application #
Study Section
Prokaryotic Cell and Molecular Biology Study Section (PCMB)
Program Officer
Gerratana, Barbara
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Georgia
Schools of Arts and Sciences
United States
Zip Code
Rocco, Christopher J; Wetterhorn, Karl M; Garvey, Graeme S et al. (2017) The PrpF protein of Shewanella oneidensis MR-1 catalyzes the isomerization of 2-methyl-cis-aconitate during the catabolism of propionate via the AcnD-dependent 2-methylcitric acid cycle. PLoS One 12:e0188130
VanDrisse, Chelsey M; Escalante-Semerena, Jorge C (2017) In Streptomyces lividans, acetyl-CoA synthetase activity is controlled by O-serine and N? -lysine acetylation. Mol Microbiol :
Burckhardt, Rachel M; Escalante-Semerena, Jorge C (2017) In Bacillus subtilis, the SatA (Formerly YyaR) Acetyltransferase Detoxifies Streptothricin via Lysine Acetylation. Appl Environ Microbiol 83:
VanDrisse, C M; Escalante-Semerena, J C (2016) New high-cloning-efficiency vectors for complementation studies and recombinant protein overproduction in Escherichia coli and Salmonella enterica. Plasmid 86:1-6
VanDrisse, Chelsey M; Hentchel, Kristy L; Escalante-Semerena, Jorge C (2016) Phosphinothricin Acetyltransferases Identified Using In Vivo, In Vitro, and Bioinformatic Analyses. Appl Environ Microbiol 82:7041-7051
Hentchel, Kristy L; Thao, Sandy; Intile, Peter J et al. (2015) Deciphering the Regulatory Circuitry That Controls Reversible Lysine Acetylation in Salmonella enterica. MBio 6:e00891
Stuecker, Tara N; Bramhacharya, Shanti; Hodge-Hanson, Kelsey M et al. (2015) Phylogenetic and amino acid conservation analyses of bacterial L-aspartate-?-decarboxylase and of its zymogen-maturation protein reveal a putative interaction domain. BMC Res Notes 8:354
Hentchel, Kristy L; Escalante-Semerena, Jorge C (2015) In Salmonella enterica, the Gcn5-related acetyltransferase MddA (formerly YncA) acetylates methionine sulfoximine and methionine sulfone, blocking their toxic effects. J Bacteriol 197:314-25
Hentchel, Kristy L; Escalante-Semerena, Jorge C (2015) Complex regulation of the sirtuin-dependent reversible lysine acetylation system of Salmonella enterica. Microb Cell 2:451-453
Mitchell, Carter A; Tucker, Alex C; Escalante-Semerena, Jorge C et al. (2015) The structure of S. lividans acetoacetyl-CoA synthetase shows a novel interaction between the C-terminal extension and the N-terminal domain. Proteins 83:575-81

Showing the most recent 10 out of 57 publications