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Báo cáo khoa học: On the mechanism of action of the antifungal agent propionate Propionyl-CoA inhibits glucose metabolism in Aspergillus nidulans

Propionate is used to protect bread and animal feed from moulds. The mode of action of this short-chain fatty acid was studied usingAspergillus nidulansas a model organism. The filamentous fungus is able to grow slowly on propio-nate, which is oxidized to acetyl-CoA via propionyl-CoA, methylcitrate and pyruvate. Propionate inhibits growth of A. nidulanson glucose but not on acetate; the latter was shown to inhibit propionate oxidation. | Eur. J. Biochem. 271 3227-3241 2004 FEBS 2004 doi 10.1111 j.1432-1033.2004.04255.x On the mechanism of action of the antifungal agent propionate Propionyl-CoA inhibits glucose metabolism in Aspergillus nidulans Matthias Brock1 and Wolfgang Buckel2 1 Laboratorium fur Mikrobiologie Universitat Hannover 2Laboratorium fur Mikrobiologie Fachbereich Biologie Philipps-Universităt Marburg Germany Propionate is used to protect bread and animal feed from moulds. The mode of action of this short-chain fatty acid was studied using Aspergillus nidulans as a model organism. The filamentous fungus is able to grow slowly on propionate which is oxidized to acetyl-CoA via propionyl-CoA methylcitrate and pyruvate. Propionate inhibits growth of A. nidulans on glucose but not on acetate the latter was shown to inhibit propionate oxidation. When grown on glucose a methylcitrate synthase deletion mutant is much more sensitive towards the presence of propionate in the medium as compared to the wild-type and accumulates 10-fold higher levels of propionyl-CoA which inhibits CoA-dependent enzymes such as pyruvate dehydrogenase succi-nyl-CoA synthetase and ATP citrate lyase. The most important inhibition is that of pyruvate dehydrogenase as this affects glucose and propionate metabolism directly. In contrast the blocked succinyl-CoA synthetase can be circumvented by a succinyl-CoA acetate propionate CoA-transferase whereas ATP citrate lyase is required only for biosynthetic purposes. In addition data are presented that correlate inhibition of fungal polyketide synthesis by pro-pionyl-CoA with the accumulation of this CoA-derivative. A possible toxicity of propionyl-CoA for humans in diseases such as propionic acidaemia and methylmalonic aciduria is also discussed. Keywords acetate CoA-transferase succinyl-CoA poly-ketide synthesis pyruvate dehydrogenase pyruvate excretion. Sodium propionate is widely used as a preservative due to its ability to inhibit fungal growth. Furthermore this .