OA-6129 D

Based on the working hypothesis that the OA-6129 group of carbapenem compounds might be the direct precursors for PS-5, epithienamycins A and C and MM 17880, Streptomyces fulvoviridis A933 17M9, a producer of PS-5, PS-6, PS-7, PS-8, epithienamycins A, B, C and D, MM 17880, MM 13902 and MM 4550, was subjected to NTG-mutation to provide a blocked mutant numbered 1501 which was found to produce OA-6129 A, OA-6129B1, OA-6129B2 and OA-6129C instead of PS-5, epithienamycins A and C and MM 17880, respectively. In a cell-free system, the parent strain demonstrated an ability to convert OA-6129A to NS-5, whereas the mutant did not. The L- and D-amino acid acylases were also shown to depantothenylate the OA-6129 group of carbapenems.

A specific acylase designated A933 acylase was isolated and purified to 90% protein homogeneity from Streptomyces fulvoviridis A933 17M9 which produces PS-5, epithienamycins A and C and MM 17880 together with minor carbapenem analogs, penicillin N and cephamycin C. This enzyme was found to catalyze the depantothenylation of OA-6129 carbapenems; the acyl exchange of OA-6129 carbapenems with acyl CoA's; the deacetylation of N-acetyl-L-amino acids; and the acylation of NS-5 and 6-aminopenicillanate with acyl CoA's, whereas the deacetylation of PS-5 and N-acetyl-D-amino acids; and the deacylation of benzylpenicillin and cephalosporin C were not observed. Similar enzyme activities were also detected in Streptomyces cattleya, Streptomyces cremeus subsp. auratilis and Streptomyces argenteolus which are all carbapenem producers.