The biosynthesis of penicillin. 8. Investigation of cyclic cysteinylvaline peptides as precursors

Abstract

The synthesis of 6-amino-2:2-dimethyl-5-oxohexahydro-l:4-thiazepine-3-carboxylic acid (cyclic DL-cysteinyl-DL-valine) and its acetyl and phenylacetyl derivatives is described. The monoacetyl and monophenylacetyl derivatives of BB-dimethyllanthionine, S-(2-acetamido-2-carboxyethyl)-DL-penicillamine and S-(2-phenylacetamido-2-carboxyethyl)-DL-penicill-amine respectively were also prepared. The compounds were tested as penicillin precursors by an isotope-competition method in which washed mycelium of Penicillium chrysogenum WIS 51-20 was incubated with L-)carboxy-C14 valine and the effect of addition of the unlabeled compounds on the specific radioactivity of the penicillin produced was measured. None of the compounds was found to be an intermediate in the conversion of valine into penicillin. Phenylacetyl-L-cysteinyl-D-valine and [beta][beta]-dimethyl-lantionine were also inactive as penicillin precursors. Possible mechanisms of penicillin biosynthesis are discussed.