Batch kinetics of Corynebacterium glutamicum during growth on various carbon substrates: use of substrate mixtures to localise metabolic bottlenecks

Abstract

Growth of Corynebacterium glutamicum on various carbon substrates has been described kinetically under batch culture conditions on fully defined medium. The use of lactate (major fermentation end-product under O₂ limitation) led to pyruvate overflow during exponential growth, although pyruvate was reconsumed late in the growth period when both specific rates and residual lactate concentration had diminished. During growth on glucose/lactate mixtures the metabolic architecture was such that simultaneous substrate consumption was observed and, in general, specific rates were correlated with mixture composition. Pyruvate overflow was, however, emphasised and correlated with the flux arriving at pyruvate, suggesting that pyruvate dehydrogenase activity may be rate-limiting under these conditions. The use of lactate/acetate mixtures, in which pyruvate overflow was not observed until all the acetate had been consumed, again suggests a metabolic bottleneck at the level of pyruvate dehydrogenase. The lack of detectable pyruvate overflow during growth on glucose, despite rapid rates of substrate consumption, can be attributed to carbon distribution through central metabolism and the tight control exerted over glucose uptake via the phosphotransferase system.