Effects of Glutamate, Glucose, Phosphate, and Alkali metal ions on cephamycin C production by Nocardia lactamdurans in defined media

Abstract

A High cephamycin C producing strain of Nocardia lactam-durans was used to study cell growth and antibiotics production in defined media. Batch fermentations in shake flasks and stirred tanks showed that antibiotic production occurred during cell growth and the production rate rapidly decline as the growth slowed. Glutamate served as a primary substrate during this phase. Later, ammonia was utilized along with a remainder of the glucose. Rapid antibiotic production occurred in this phase. Increased glutamate promoted higher growth, a rise in ammonium ion concentration, and a marked reduction in antibiotic titers. An increase of the glucose concentration along with the glutamate concentration balanced to the medium; no ammonium ion rise occurred and a peak specific antibiotic titer comparable to the control medium was obtained. In a phosphate-limited medium, cell growth equivalent to the control medium and increased antibiotic titers were obtained. In these experiments, adjustment of Na(+) and K(+) ion concentration equal to that in the control medium was found to be important. Based on carbon and nitrogen balances, the activity of the key nitrogen metabolism enzymes, and the published literature, a two-stage model of regulation is suggested.

Application of oxygen uptake rate and response surface methodology for erythromycin production by Saccharopolyspora erythraea

“…as a cofactor can regulate the enzyme activity of metabolic pathway [11,12]. Many secondary metabolites were derived from amino acids which were usually used as precursor for enhancing production of antibiotics [13]. A total of five variables were analyzed with regard to their effects on erythromycin production using a fractional factorial design ( Table 1).…”

Actinomycetes scale‐up for the production of the antibacterial, nocathiacin

“…This lack of distinct trophophase and idiophase separation was similar to that of vancomycin; interestingly, for vancomycin, separation was created by adding excess phosphate but this also delayed production onset and depressed production by 95% (Mertz and Doolin,1973). Observed nocathiacin kinetics were in contrast with those of other actinomycetes fermentations: Cephamycin C production by Nocardia lactamdurans was highest during the cell growth phase and rapidly declined as growth slowed (Kirpekar et al,1991). When carbon or nitrogen assimilation limited growth rate, actinorhodin production by Streptomyces coelicolor occurred during the period of biomass accumulation, but high growth rates often delayed product synthesis until biomass accumulation was completed (Liao et al,1995).…”

“…It was similar to typical Nocardia/Amycolatop-sis pH profiles which initially are neutral, then became alkaline during the growth phase (likely owing to carbohydrate and accumulated intermediate organic acid metabolism, and appearance of nitrogen by-products such as ammonium from metabolized proteins). Broth pH then decreases, in some cases becoming acidic, as ammonium levels decrease, organic acids are produced, and secondary metabolite production begins (Jain et al, 1992;Kirpekar et al, 1991;Lee et al, 1983). Owing to the tendency of the P-148 culture to produce ammonia in Noc-0111 medium and thus raise broth pH, pH was controlled at 7.8-8.0 vs. the base case of 6.8-7.0 in one fermentation.…”