Microbiological Aspects of Penicillin

Abstract
Different strains of P. notatum differ markedly in penicillin-producing ability, and selection of the most potent strains is of primary importance for maximum penicillin production. Active strains tend to degenerate or lose their capacity to produce penicillin, especially after continued serial transfer on laboratory media. This degeneration can be eliminated by reducing vegetative transfers, and a practical system for doing this is described. Plating procedures on active cultures yield isolates with different degrees of penicillin activity. Under conditions where the acidity of the medium reaches pH 3-4 and remains there for some time before rising, notatin is formed by P. notatum. Penicillin is produced when the pH does not fall so low and rises rapidly to 6-8.5. Extreme purity of the medium ingredients induces the appearance of the low pH and formation of notatin. The presence of certain trace elements, notably zinc under these conditions, and also organic supplements, favors the rapid rise in pH and formation of penicillin. Zinc in particular acts in this manner by catalyzing the complete oxidation and utilization of glucose by the mold, thus preventing the accumulation of gluconic acid which is responsible for the fall in pH of the medium.