Some characteristics of p‐fluorophenylalanine‐resistant mutants of Penicillium cyclopium

p-Fphe-resistant mutants of Penicillium cyclopium Westling were selected by the gradient method of SZYBALSKI. The strains grow well in the presence of 1 mg p-Fphe/ml1) nutrient agar. However, sporulation decreases considerably after repeated subcultivation on this medium. Drug resistance in the mutant strains seems to depend on reduced p-Fphe incorporation into proteins. Radioactivity of 3H-p-Fphe added to cultures is incorporated into the proteins of the mutants at a lower rate compared with the wild type strain. Furthermore, in spite of the fact that also in the wild type strain part of the p-Fphe is transformed into phe, the ratio of 3H-p-Fphe to 3H-phe in the proteins after feeding of labelled p-Fphe is lower in the mutant. Addition of 100 μg/ml of p-Fphe to the nutrient solution of the strain res-p-Fphe 11 does not influence hyphal growth but reduces alkaloid production and sporulation. Thus processes of cell specialization in P. cyclopium, as in other microorganisms, are more sensitive to the synthesis of abnormal proteins than processes of basic growth. Simultaneous feeding of p-Fphe and tyr increases the p-Fphe effects due to a stimulated uptake of the drug. In the p-Fphe-resistant mutants the internal level of free phe exceeds that of the wild type strain. Also phe and a small amount of tyr is excreted into the nutrient solution. In spite of the fact that external phe added to the cultures under certain conditions increases alkaloid production in P. cyclopium, mutants and wild type strains produce the same alkaloid amount. This result is discussed with regard to the cellular compartmentation of phe.