Metabolism of d -Serine in Escherichia coli K-12: Mechanism of Growth Inhibition

Abstract

Without significant killing, d -serine at concentrations greater than 50 μg/ml inhibits growth in minimal media of mutants of Escherichia coli K-12 unable to form d -serine deaminase. The mutants eventually recover at lower concentrations. There is no evidence of d -serine toxicity in rich media. Toxicity is partially reversed by l -serine. d -Serine does not interfere with l -serine activation, one-carbon metabolism, or (Cronan, personal communication) formation of phosphatidylserine. Pizer (personal communication) finds, however, that it is a powerful feedback inhibitor of the first enzyme of l -serine biosynthesis. In the presence of l -serine, the residual toxicity is largely and noncompetitively over come by pantothenate, indicating that d -serine inhibits growth by affecting two targets: pantothenate biosynthesis and l -serine biosynthesis. l -Serine causes transient growth inhibition in E. coli K-12. Contaminating l -serine in d -serine preparations contributes to the d -serine inhibitory response.