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J Biol Chem. 2015 Sep 18;290(38):23064-76. doi: 10.1074/jbc.M115.648642. Epub 2015 Jul 30.

Regulation of Ergothioneine Biosynthesis and Its Effect on Mycobacterium tuberculosis Growth and Infectivity.

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  • 1From the Division of Infectious Diseases, Department of Medicine and.
  • 2Kwazulu-Natal Research Institute for Tuberculosis and HIV, Durban, South Africa 4001.
  • 3Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia V6H 3Z6, Canada.
  • 4Institute of Modern Biopharmaceuticals, School of Life Sciences, Southwest University, Chongqing 400715, China, and.
  • 5Kwazulu-Natal Research Institute for Tuberculosis and HIV, Durban, South Africa 4001, Department of Microbiology and Centers for AIDS Research and Free Radical Biology, University of Alabama, Birmingham, Alabama 35233.
  • 6From the Division of Infectious Diseases, Department of Medicine and


Ergothioneine (EGT) is synthesized in mycobacteria, but limited knowledge exists regarding its synthesis, physiological role, and regulation. We have identified Rv3701c from Mycobacterium tuberculosis to encode for EgtD, a required histidine methyltransferase that catalyzes first biosynthesis step in EGT biosynthesis. EgtD was found to be phosphorylated by the serine/threonine protein kinase PknD. PknD phosphorylates EgtD both in vitro and in a cell-based system on Thr(213). The phosphomimetic (T213E) but not the phosphoablative (T213A) mutant of EgtD failed to restore EGT synthesis in a ΔegtD mutant. The findings together with observed elevated levels of EGT in a pknD transposon mutant during in vitro growth suggests that EgtD phosphorylation by PknD negatively regulates EGT biosynthesis. We further showed that EGT is required in a nutrient-starved model of persistence and is needed for long term infection of murine macrophages.


Mycobacterium tuberculosis; bacterial protein kinase; bacterial signal transduction; ergothioneine; histidine methylation; microbiology; thiol

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