The biosynthesis of penicillin. 2. The incorporation of cystine into penicillin

Abstract

The preparation of L- and D-cystine, labelled with Cl14 in the beta-position, N15 or S35 is described. By appropriate dilution with unlabelled carrier, each optically active form was obtained practically free from labelled enantiomorph. The conversion of L- and D-(beta-C14, n15, s35). and L- (beta-C14, s35)-cystine into penicillin and into the cystine of the mycelial protein was studied. Penicillin and cysteic acid from the mycelial cystine were chemically degraded in order to ascertain the distribution of the isotopes. The labelled L-cystine was a more efficient precursor of penicillin and of mycelial cystine than the D enantiomorph. The ratios of the C14, Nl5 and S35 isotopes in the mycelial cystine and in the labelled atoms of penicillin were identical and similar to those of the L-cystine which were added to the fermentation. It is concluded that cystine is a direct precursor of penicillin, probably after reduction to cysteine. Its role in penicillin biosynthesis is discussed.