Ferrero M A, Reglero A, Martín-Villacorta J, Fernández-Cañón J M, Luengo J M
Departmento de Bioquímica y Biología Molecular, Universidad de León, España.
J Antibiot (Tokyo). 1990 Jun;43(6):684-91. doi: 10.7164/antibiotics.43.684.
"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 gamma-glutamyl cycle are directly involved in the biosynthesis of penicillins. To explain "in vivo" formation of this beta-lactam antibiotic, a biosynthetic pathway which includes several glutathione-S-derivatives and a non-enzymatic reaction, is proposed.
通过用S-苯乙酰基谷胱甘肽和（S-苯氧乙酰基）谷胱甘肽对6-氨基青霉烷酸（6-APA）进行直接N-酰化反应，已实现了苄青霉素和苯氧甲基青霉素的“体外”合成。这些反应由产黄青霉的酰基辅酶A：6-APA酰基转移酶（AT）催化，并且在这两种情况下，辅酶A均能增强抗生素的合成。天然青霉素青霉素K也通过将（S-辛酰基）谷胱甘肽、6-APA和AT一起孵育而“体外”合成，但在这种情况下，抗生素的形成需要辅酶A的存在。此外，苄青霉素是由（S-苯乙酰基）半胱氨酰甘氨酸和6-APA制得的，这表明γ-谷氨酰循环的一些中间体直接参与了青霉素的生物合成。为了解释这种β-内酰胺抗生素的“体内”形成过程，提出了一种包括几种谷胱甘肽-S-衍生物和一个非酶反应的生物合成途径。
