The biosynthesis of penicillin. 1. The incorporation of some amino acids into penicillin

Abstract

The conversion of (alpha-C14)glycine, DL-(beta-C14)-serine, DL-, D-and L-(beta-C14) cystine and DL-(gamma-C14)-valine into penicillin was studied by adding the labeled amino acids to fermentations of Penicillium chrysogenum WIS 48-701. Valine was found to be a precursor of the penicillamine moiety of penicillin, whereas cystine and to a lesser extent glycine were incorporated into the beta-lactam ring of the molecule. Penicillin biosynthesis from cystine appears to be stereochemically specific, L-cystine being utilized to a far greater extent than the D enantiomorph. The highest incorporation of radioactivity from cystine into penicillin was obtained when the amino acid was added to the fermentation at 23-47 hrs. after inoculation. The slight dilution of the specific radioactivity of cystine during its conversion into penicillin suggests that cysteine may be an important and direct precursor of penicillin.