The effect of certain enzyme inhibitors on respiration and on penicillin formation by Penicillium chrysogenum.

Abstract

Summary: The effect of phenol, mercuric chloride, fluoride, bisulphite, azide, malonate, 2:4-dinitrophenol and cyanide on respiration and penicillin production was studied using suspensions of washed penicillin-producing mycelium of Penicillium chrysogenum in Warburg flasks. Inhibition of penicillin production by phenol and by mercuric chloride closely followed the inhibition of respiration. Both fluoride and bisulphite inhibited penicillin production to a greater extent than respiration. Malonate was without effect on respiration or penicillin production, possibly because the pH was too high to allow a sufficient concentration of undissociated acid. Penicillin production was inhibited by 2:4-dinitrophenol at concentrations which had little effect on respiration, suggesting that phosphate bond energy is utilized in penicillin formation. Penicillin production was extremely sensitive to cyanide. A concentration of 0·000002 m-KCN, which caused no significant inhibition of respiration, depressed the rate of penicillin production to c. 25% of normal. Maximum rates of penicillin production and respiration are dependent on cyanide-sensitive systems but an alternative, relatively cyanide-stable system allows both respiration and penicillin production to proceed at c. 25% of the maximum rate.