Antibiotic yield

To obtain reproducible antibiotic production by fermentation, it is necessary to obtain a pure culture of the producing organism. Pure cultures are isolated from mixed soil sample populations by various streaking and isolation techniques on nutrient media. Once a pure culture has been found that produces a new antibiotic typically on a mg/L scale, improvement in antibiotic yield is accompHshed by modification of the fermentation medium or strain selection and mutation of the producing organism. Production of g/L quantities may take years to accomplish. 

Occasionally courts speak about a single-idea invention, and there is a presumption that with such single-idea inventions, joint inventorship is unlikely. An example would be a known biological method for producing an antibiotic. The antibiotic yield is increased by, say, merely raising the temperature. It would be difficult to argue that this is a joint invention. 

Merck process chemists showed that an acid-regulated, one-pot transformation of a cephalosporin derivative to the antibiotic cefoxitin was complex (Weinstock, 1986). Not only did it entail eight discrete chemical reactions at least, but some of them had to occur synchronously to maximize the antibiotic yield. Moreover, the concentration of hydrochloric acid reached an optimum at 0.004 molar. The rates of some of the eight reactions were proportional to this concentration and others to its square. 

A Polish patent (7 1) claims that, in rifamycin B production, by decreasing the stirrer circumference speed from 260-310 to 100-20 m/min during vegetative culture and to 160-90 tn/min in the production phase, it is possible to prevent mycelium fragmentation and pH drop, to retard sugar consumption, and to decrease the mycelial mass. This leads to a consistent increase of the antibiotic yield. 

Hydrolysis of flavumycin A, an aromatic heptaenic antibiotic, yielded mycos-amine (3-amino-3,6-dideoxy-D-mannose) and 4-acetylaniline. ... 

Microbiological processes for production of cephalosporin C resemble in many respects those used for penicillin production. Special strains of Cephalosporium have been selected that produce more cephalosporin C and less cephalosporin N than the parent culture. The growth of these strains in certain special fermentation media has resulted in higher antibiotic titers. Even with these improvements in processing, the antibiotic yields, averaging 10 to 20g/liter, are much lower than those reported for the penicillins. Cephalosporins sell for around 250/kg. 

Of nine metallic ions examined, only Mn+ is required for bacitracin synthesis at a concentration different than for vegetative growth (Table 2). The concentration of Mn+ is critical for the synthesis of a wide variety of secondary metabolites by species of Bacillus (Weinberg, 1964). In the recipes for commercial production of bacitracin, soybean meal is generally included to obtain maximal cell and antibiotic yields (Hickey, 1964). Soybean meal contains approximately 30(xg Mn+2 per gram (Spector, 1956) and its activity may be due in part to the fact that, at the usual concentration of 4%, it contributes about 2 X 10 M Mn+ to the fermentation medium. In experiments in which protoplasts (Snoke, I96I)... 

As shown in Table 4, optimal production of polymyxin D by B. polymyxa strain Lederle B7I occurred with 0.5% yeast extract and 2% ammonium sulfate as the nitrogen source, whereas tryptone or tryp-tone plus yeast extract, which support growth as well or better than yeast extract plus ammonium sulfate, afford little or no polymyxin production. The carbon source is less critical for antibiotic yield glucose. 

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