BIOSYNTHESIS OF BENZYLPENICILLIN (G), PHENOXYMETHYLPENICILLIN (V) AND OCTANOYLPENICILLIN (K) FROM GLUTATHIONE S-DERIVATIVES .5.

“In vitro” synthesis of benzylpenicillin and phenoxymethylpenicillin has been carried out by direct N-acylation of 6-aminopenicillanic acid (6-APA) with S-phenylacetyl- and (S-phenoxyacetyl)glutathione. The reactions were catalyzed by the enzyme acyl-CoA: 6-APA acyltransferase (AT) from Penicillium chrysogenum and in both cases the synthesis of antibiotics was enhanced by CoA. Penicillin K, a natural penicillin, was also synthesized “in vitro” by incubating (S-octanoyl)glutathione, 6-APA and AT, but in this case the formation of antibiotic required the presence of CoA. Furthermore, benzylpenicillin was obtained from (S-phenylacetyl)cysteinylglycine and 6-APA, suggesting that some intermediates of the γ-glutamyl cycle are directly involved in the biosynthesis of penicillins. To explain “in vivo” formation of this β-lactam antibiotic, a biosynthetic pathway which includes several glutathione-S-derivatives and a non-enzymatic reaction, is proposed. © 1990, JAPAN ANTIBIOTICS RESEARCH ASSOCIATION. All rights reserved.