Selection of strains of Penicillium chrysogenum with reduced penicillin yields in continuous cultures

In sucrose‐limited chemostat cultures of high‐yielding strains of Penicillium chrysogenum the ability to produce penicillin was progressively lost. Subcultures from the chemostats on to agar showed a progressive increase in the proportion of non‐conidiating colonies, designated the D‐phenotype, which produced low yields of penicillin in shake‐flask tests. When the growth‐limiting substrate was ammonia, phosphate or sulphate, production of penicillin was maintained and the D‐phenotype did not appear. However, when a mutant with the D‐phenotype was inoculated into an ammonia‐limited culture of the parent strain, it quickly displaced the parent. The mutant had a yield constant for ammonia 44% higher than had the parent. The conclusion reached is that growth‐limitation by the carbon source is necessary for the occurrence of the mutation or for the initial stages of selection.