Regulatory mechanism of primary metabolism responsible for the biosynthesis of peptide ergot alkaloids was proposed on the basis of experimental results from the production phase of Claviceps purpurea (FR.) Tul. in parasitic and saprophytic cultures. The production-phase metabolism is characterized by uncoupling of glycolysis from the citric acid cycle and by a break in this cycle at the level of the 2-exoglutarate dehydrogenase complex. This regulation is due to the inhibition by citrate and malate, i.e. the final products continuously taken up from the external medium. The rate of the intact reaction steps of the citric acid cycle is therefore not limited by the actual acetyl-CoA or oxaloacetate pool. The regulation also leads to an excessive synthesis of acetyl-CoA, 2-oxoglutarate and oxaloacetate, which represent the key metabolites of primary metabolism, and to their utilization in the biosynthesis of peptide alkaloids.

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