VANCOMYCIN PRODUCTION IN BATCH AND CONTINUOUS-CULTURE

Production of the glycopeptide antibiotic vancomycin by two Amycolatop sis orientalis strains was examined in batch shake flask culture in a semidefined medium with peptone as the nitrogen source. Different grow th and production profiles were observed with the two strains; specifi c producion (Yp/x) was threefold higher with strain ATCC 19795 than wi th strain NCIMB 12945. A defined medium with amino acids as the nitrog en source was developed by use of the Plackett-Burman statistical scre ening method. This technique identified certain amino acids (glycine, phenylalanine, tyrosine, and arginine) that gave significant increased specific production, whereas phosphate was identified as inhibitory f or high specific vancomycin production. Experiments made with the impr oved medium and strain ATCC 19795 showed that vancomycin production ki netics were either growth dissociated or growth associated, depending on the amino acid concentration. In chemostat culture at a constant di lution rate (0.087 h(-1)), specific vancomycin production rate (q(vanc omycin)) decreased linearly as the medium phosphate concentration was increased from 2 to 8 mM. In both phosphate and glucose limited chemos tats, q(vancomycin) was a function of specific growth rate; the maximu m value was observed at D = 0.087 h(-1) (52% of the maximum specific g rowth rate). Under phosphate limited growth conditions, qvani, was thr eefold higher (0.37 mg/g dry weight/h) than under glucose limitation ( 0.12 mg/g dry weight/h). (C) 1996 John Wiley & Sons, Inc.