BIOSYNTHESIS OF UNNATURAL CEPHALOSPORINS

摘要

A process for producing unnatural penicillins and cephalosporin derivatives thereof in which peptide analogs of ACV in which the L- alpha -aminodipyl moiety is replaced by L-S-carboxymethyl cysteine or other substituents, are reacted with cyclase, epimerase and ring expansion enzyme isolated from a cell free extract of a prokaryotic organism such as S. clavuligerus. The product depends upon the presence or absence of co-factors such as ferrous ion, alpha -ketoglutarate, and ascorbate. In an alternative embodiment, a penicillin analog having the formula may be reacted with L-cysteine to produce an analog of isopenicillin N which may be reacted with the enzyme reagent to produce the desired penicillin or cephalosporin.