I. UPTAKE OF PHENYLACETIC ACID BY PENICILLIUM CHRYSOGENUM WIS 54-1255: A CRITICAL REGULATORY POINT IN BENZYLPENICILLIN BIOSYNTHESIS

The transport system of phenylacetic acid (PA) in Penicillium chrysogenum was studied. Kinetic measurements were carried out "in vivo" at 25°C in 0.06 M phosphate buffer at pH 6.5. Uptake was a linear function of time over 3 minutes and the Km was 5.2μM. PA uptake was inhibited by 2, 4-dinitrophenol, 4-nitrophenol, sodium azide, potassium cyanide, N-ethylmaleimide, amino acids, xylose and fatty acids whereas lactose and ribose stimulated it. Benzylpenicillin, phenoxymethylpenicillin, penicillins DF, K and 6-aminopenicillamc acid did not modify uptake whereas phenoxyacetic acid and many phenyl derivatives strongly inhibited the incorporation of PA. PA transport is an inducible system that is strictly regulated by the carbon source used for P. chrysogenum growth. Uptake is not induced by phenoxyacetic acid and is repressed by L-lysine. The absence of the PA transport system when P. chrysogenum is grown in the presence of readily metabolized sugars and its repression by L-lysine suggests that this is a critical regulatory point in the control of benzylpenicillin biosynthesis.