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Cell-free extracts prepared by sonication of Streptomyces clavuligerus cyclized delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine (ACV) into a penicillin-type antibiotic. The antibacterial spectrum of this antibiotic suggested it was a mixture of isopenicillin N and penicillin N indicating that both cyclization and racemase activities were present. Cyclization activity was optimal in extracts prepared from 48 hours cultures. Extracts incubated at 20 degrees C produced antibiotic for 2 hours before activity ceased. Cyclization activity showed an absolute requirement for dithiothreitol (DTT) and O2 and was stimulated by ascorbic acid and FeSO4. No requirement for ATP was observed.

Cyclization of .DELTA.-(L-.ALPHA.-aminoadipyl)-L-cysteinyl-D-valine to penicillins by cell-free extracts of Streptomyces clavuligerus.