Conversion of Cephalosporins to 7a-Methoxycephalosporins by Cell-Free Extracts of Streptomyces clavuligerus

In the presence of S-adenosylmethionine, 2-oxoglutarate, Fe2+ and a reducing agent, cell-free extracts of Streptomyces clavuligerus convert cephalosporin C and 0carbamoyldeacetylcephalosporin C into 7a-methoxy derivatives. No synthesis of a 7a-methoxy derivative of deacetylcephalosporin C was detected in the system used, and the 7a-methoxy derivative of deacetoxycephalosporin C was produced only in relatively small amounts. It appears that the 7a-methoxy group is introduced after the cephalosporin ring system has been formed and that its introduction may represent the final step in a biosynthetic pathway.