INDUCED VARIATION AND STRAIN SELECTION OF PENICILLIUM CHRYSOGENUM IN RELATION TO TITER OF NATURAL PENICILLINS

Penicillium chrysogenum strain Wisconsin Q176 was used as the parent for a sequence of six experiments in combined irradiation and selection of strains yielding high titers of penicillin with N-(2-hydroxyethyl)-phenylacetamide as the precursor for benzylpenicillin. Altogether, 124 colonies were tested. The six strains chosen as best in their respective experiments were compared. Visible changes were found in color and amount of sporulation and in loss of the deep yellow pigment characteristic of fermentation with Q176. Under standard conditions of test, the peak titer of total penicillin increased in a stepwise fashion from 1285 units/ml. to 2575 units/ml. With appropriate medium, the best strain produced nearly 3000 units/ml., of which more than 95% was benzylpenicillin. In the absence of added precursor, the percentage of p-hydroxybenzylpenicillin produced by new isolates increased from 13% of 600 units/ml. to more than 30% of 1000 units/ml. The amount of penicillin F was quite constant, while that of other types was not changed with any apparent regularity. The change in reaction during rapid production of penicillin differed in the degree of acidity noted. When other common precursors for benzylpenicillin were used, about 50% more total penicillin was found than in the control without precursor. The total titer was never as high as with suitable amounts of the particular precursor which had been used in isolating the strains. With each irradiation experiment, the strain deemed best showed increased ability to convert the chosen precursor to benzylpenicillin.