The synthesis of methionine by suspensions of Escherichia coli.

The first indication that p-aminobenzoic acid is concerned in the synthesis of methionine by microorganisms was the observation that methionine, under appropriate conditions, overcame inhibition of growth by sulphonamides in a non-competitive manner (Harris & Kohn, 1941; Kohn, 1943; Bliss & Long, 1941). Since then methionine has frequently been shown with various organisms to be an essential component of mixtures which replace paminobenzoic acid either in overcoming sulphonamide inhibition or in supporting growth of organisms requiring this vitamin (e.g. Lampen, Jones & Roepke, 1949; Strehler, 1950; Cutts & Rainbow, 1950). There is thus strong presumptive evidence that p-aminobenzoic acid has a function at one or more steps in methionine synthesis. A role for cobalamin in the same synthesis was first found by Davis & Mingioli (1950), who isolated mutants of E8cherichia coli requiring for growth either methionine or cobalamin; the relative concentrations required suggested that cobalamin might function as a catalyst in the synthesis of methionine. Studies of the nutritional properties of mutant strains ofbacteria and moulds requiring methionine for growth have provided strong presumptive evidence that this amino acid is derived from cysteine through the intermediary formation of cystathionine and homocysteine; the last step is thus the methylation of homocysteine (Horowitz, 1947; Teas, Horowitz & Fling, 1948; Lampen, Roepke & Jones, 1947; Gots & Koh, 1950; Gots, 1951; Plough, Miller & Berry, 1951). Since homocysteine will not replace methionine in the sparing of either p-aminobenzoic acid or cobalamin, it is likely that the function of both these vitamins is at the last, or methylation, step in the formation of methionine. The work of Emerson (1950) with Neurospora suggests that this stage may be complex. The object of the present work was to obtain a simpler system for the synthesis of methionine than the whole growing culture, and one in which all the reactants could be clearly defined. It should then be possible to study with greater precision the roles of p-aminobenzoic acid and cobalamin, and to