Homocysteine editing and growth inhibition in Escherichia coli.
In Escherichia coli homocysteine (Hcy) is metabolically converted to the thioester Hcy-thiolactone in ATP-consuming reactions catalysed by methionyl-, isoleucyl- and leucyl-tRNA synthetases. Here we show that growth inhibition caused by supplementation of E. coli cultures with Hcy is accompanied by greatly increased accumulation of Hcy-thiolactone. Energy dissipation for Hcy editing increases 100-fold in the presence of exogenous Hcy and reaches one mole of ATP unproductively dissipated for Hcy-thiolactone synthesis per each mole of ATP that is consumed for methionine activation. Inhibiting Hcy-thiolactone synthesis with isoleucine, leucine or methionine accelerates bacterial growth in Hcy-supplemented cultures. Growth rates in Hcy-inhibited cultures are inversely related to the accumulation of Hcy-thiolactone. We also show that the levels of protein N-linked Hcy modestly increase in E. coli cells in Hcy-supplemented cultures. The results suggest that Hcy editing restrains bacterial growth.
Sikora
Marta
M
Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznań, Poland.|Department of Microbiology and Molecular Genetics, UMDNJ-New Jersey Medical School, International Center for Public Health, Newark, NJ 07101, USA.
Jakubowski
Hieronim
H
Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznań, Poland.|Department of Microbiology and Molecular Genetics, UMDNJ-New Jersey Medical School, International Center for Public Health, Newark, NJ 07101, USA.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000604:Amino Acyl-tRNA Synthetases / Q000378:metabolism; D004734:Energy Metabolism; D004926:Escherichia coli / Q000254:growth & development / Q000378:metabolism; D006710:Homocysteine / Q000031:analogs & derivatives / Q000096:biosynthesis / Q000378:metabolism*; D007532:Isoleucine / Q000378:metabolism; D007930:Leucine / Q000378:metabolism; D008715:Methionine / Q000378:metabolism; D014176:Protein Biosynthesis; D019346:Sodium Acetate / Q000378:metabolism
D007532:Isoleucine; D006710:Homocysteine; D019346:Sodium Acetate; D000255:Adenosine Triphosphate; D008715:Methionine; C007957:homocysteine thiolactone; D000604:Amino Acyl-tRNA Synthetases; D007930:Leucine