This study examined how Escherichia coli K12 can be induced to grow on L-serine as a sole carbon source, despite wild-type strains being unable to do so. The researchers identified two distinct mechanisms. First, metJ mutants—which constitutively express methionine biosynthetic enzymes—can grow on L-serine. Importantly, a plasmid carrying only the metC gene (encoding cystathionine β-lyase) is sufficient to confer this ability, suggesting that L-serine degradation occurs as a side reaction of this enzyme. L-serine deaminase (L-SD) is not required for this growth. Second, two independently isolated mutants (gos-3 and gos-5) map to positions 89.6-90 minutes on the chromosome and can grow on L-serine at 28°C while requiring methionine at elevated temperatures. These gos mutants differ from metJ mutants and histidine-constitutive mutants in key enzymatic and phenotypic properties, suggesting they represent a distinct metabolic perturbation. The work reveals unexpected connections between L-serine metabolism and methionine biosynthesis and indicates that multiple genetic pathways can enable L-serine utilization in E. coli.

Key findings

• MetJ regulatory mutants constitutive for methionine biosynthesis can grow on L-serine without elevated L-serine deaminase activity, and a metC plasmid alone is sufficient to confer this phenotype
• Cystathionine β-lyase (metC gene product) can catalyze L-serine deamination as a side reaction, allowing L-serine utilization independent of L-serine deaminase
• Two novel conditional methionine auxotroph mutants (gos-3 and gos-5) map to 89.6-90 minutes and enable L-serine growth at 28°C through a mechanism distinct from metJ mutations
• The gos mutants are not constitutive for methionine or histidine biosynthetic enzymes and show differential sensitivity to glutamyl-γ-methyl ester, indicating a novel genetic lesion