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Pathway Description
Glycine metabolism: kbl, tdh
Escherichia coli K-12
Category:
Metabolite Pathway
Sub-Category:
Signaling
Created: 2025-03-13
Last Updated: 2025-06-26
The regulation of the kbl, tdh operon. The operon is activated by gcvA (Glycine cleavage system transcriptional activator) and inhibited when gcvR (Glycine cleavage system transcriptional repressor) also binds to the promoter. GcvA binds to the promoter providing the affinity or shape needed for crp to bind to the promoter. When gcvR also binds to the promoter, the conditions for crp to bind are no longer optimal and it cannot transcribe the operon. Glycine concentrations also play a role in whether the operon is inhibited or activated. High concentrations of glycine inhibit the operon, while low concentrations of glycine activate the operon. The products of this operon are two enzymes: kbl (2-amino-3-ketobutyrate coenzyme A ligase) and tdh (L-threonine 3-dehydrogenase). Both enzymes are used in a two step process to degrade threonine to glycine. Tdh is used in the first step to change threonine to (2S)-2-amino-3-oxobutanoate. Kbl is used in the second step to change (2S)-2-amino-3-oxobutanoate to glycine.
References
Glycine metabolism: kbl, tdh References
Motoyama T, Nakano S, Hasebe F, Miyata R, Kumazawa S, Miyoshi N, Ito S: Chemoenzymatic synthesis of 3-ethyl-2,5-dimethylpyrazine by L-threonine 3-dehydrogenase and 2-amino-3-ketobutyrate CoA ligase/L-threonine aldolase. Commun Chem. 2021 Jul 16;4(1):108. doi: 10.1038/s42004-021-00545-8.
Pubmed: 36697628
Adjogatse E, Bennett J, Guo J, Erskine PT, Wood SP, Wren BW, Cooper JB: The X-ray structure of L-threonine dehydrogenase from the common hospital pathogen Clostridium difficile. Acta Crystallogr F Struct Biol Commun. 2021 Aug 1;77(Pt 8):269-274. doi: 10.1107/S2053230X21007135. Epub 2021 Jul 28.
Pubmed: 34341193
Ernsting BR, Atkinson MR, Ninfa AJ, Matthews RG: Characterization of the regulon controlled by the leucine-responsive regulatory protein in Escherichia coli. J Bacteriol. 1992 Feb;174(4):1109-18. doi: 10.1128/jb.174.4.1109-1118.1992.
Pubmed: 1346534
Heil G, Stauffer LT, Stauffer GV: Glycine binds the transcriptional accessory protein GcvR to disrupt a GcvA/GcvR interaction and allow GcvA-mediated activation of the Escherichia coli gcvTHP operon. Microbiology (Reading). 2002 Jul;148(Pt 7):2203-2214. doi: 10.1099/00221287-148-7-2203.
Pubmed: 12101307
Aronson BD, Somerville RL, Epperly BR, Dekker EE: The primary structure of Escherichia coli L-threonine dehydrogenase. J Biol Chem. 1989 Mar 25;264(9):5226-32.
Pubmed: 2647748
Sofia HJ, Burland V, Daniels DL, Plunkett G 3rd, Blattner FR: Analysis of the Escherichia coli genome. V. DNA sequence of the region from 76.0 to 81.5 minutes. Nucleic Acids Res. 1994 Jul 11;22(13):2576-86. doi: 10.1093/nar/22.13.2576.
Pubmed: 8041620
Blattner FR, Plunkett G 3rd, Bloch CA, Perna NT, Burland V, Riley M, Collado-Vides J, Glasner JD, Rode CK, Mayhew GF, Gregor J, Davis NW, Kirkpatrick HA, Goeden MA, Rose DJ, Mau B, Shao Y: The complete genome sequence of Escherichia coli K-12. Science. 1997 Sep 5;277(5331):1453-62. doi: 10.1126/science.277.5331.1453.
Pubmed: 9278503
Wilson RL, Stauffer GV: DNA sequence and characterization of GcvA, a LysR family regulatory protein for the Escherichia coli glycine cleavage enzyme system. J Bacteriol. 1994 May;176(10):2862-8. doi: 10.1128/jb.176.10.2862-2868.1994.
Pubmed: 8188587
Everett M, Walsh T, Guay G, Bennett P: GcvA, a LysR-type transcriptional regulator protein, activates expression of the cloned Citrobacter freundii ampC beta-lactamase gene in Escherichia coli: cross-talk between DNA-binding proteins. Microbiology. 1995 Feb;141 ( Pt 2):419-30. doi: 10.1099/13500872-141-2-419.
Pubmed: 7704273
Burland V, Plunkett G 3rd, Sofia HJ, Daniels DL, Blattner FR: Analysis of the Escherichia coli genome VI: DNA sequence of the region from 92.8 through 100 minutes. Nucleic Acids Res. 1995 Jun 25;23(12):2105-19. doi: 10.1093/nar/23.12.2105.
Pubmed: 7610040
Hayashi K, Morooka N, Yamamoto Y, Fujita K, Isono K, Choi S, Ohtsubo E, Baba T, Wanner BL, Mori H, Horiuchi T: Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110. Mol Syst Biol. 2006;2:2006.0007. doi: 10.1038/msb4100049. Epub 2006 Feb 21.
Pubmed: 16738553
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