Purification and Characterization of the Isopenicillin N Synthase of Streptomyces lactamdurans

Abstract
The isopenicillin N synthase (cyclase) of Streptomyces lactamdurans (syn. Nocardia lactamdurans) has been purified to near homogeneity as judged by SDS-PAGE and isoelectric focusing. This enzyme catalyses the oxidative cyclization of the tripeptide .delta.-(L-.alpha.-aminoadipyl)-L-cysteinyl-D-valine to isopenicillin N. The enzyme required DTT, Fe2+ and oxygen and it was greatly stimulated by ascorbic acid. It was strongly inhibited by Co2+, Zn2+ and Mn2+. Optimal pH and temperature were 7.0 and 25.degree.C (with the assay conditions used), respectively. The apparent Km of isopenicillin N synthase for .delta.-(L-.alpha.-aminoadipyl)-L-cysteinyl-D-valine was 0.18 mM. The enzyme is a monomer with an Mr of 26500 .+-. 1000 and a pI of 6.55.

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