IMPROVED OXYGEN-TRANSFER IN CULTURES OF NOCARDIA-LACTAMDURANS MAINTAINS THE CEPHAMYCIN BIOSYNTHETIC PROTEINS FOR PROLONGED TIME AND ENHANCES THE CONVERSION OF DEACETYLCEPHALOSPORIN INTO CEPHAMYCIN-C

Batch cultures of Nocardia lactamdurans MA4213 in stirred tank ferment ers (400 rpm) became oxygen limited after 45 h of incubation. When the stirrer speed was increased at 36 h from 400 to 600 rpm there was a 5 -fold increase in the dissolved oxygen (DO) in the broth what resulted in a 2-fold stimulation of cephamycin biosynthesis. Immunoblotting st udies using antibodies against the alpha-aminoadipyl-cysteinyl-valine synthetase and the protein P7 (cephem-7-hydroxylase) component of the methoxylation system showed that cultures with increased DO concentrat ions maintained high levels of these proteins for an extended period o f time. Under these conditions there was an enhanced conversion of cep hamycin intermediates into cephamycin C. Allophane and alumina exerted a strong stimulatory effect on cephamycin biosynthesis that correlate d with high DO levels in allophane-or alumina-supplemented cultures at low agitation speeds. Allophane or alumina supplementation of N. lact amdurans cultures resulted in a delayed decay of the cephem-7-hydroxyl ase protein in the cells favoring conversion of the cephamycin interme diates into cephamycin C. (C) 1997 Elsevier Science B.V.