A Semi-Stoichiometric Model for a Streptomyces Fed-Batch Cultivation with Multiple Feeds

A semi-stoichiometric model has been developed for the clavulanic acid (CA) production by Streptomyces clavuligerus in a fed-batch process on a chemically defined medium. Six fed-batch cultivations were performed with a similar batch medium containing glycerol, glutamate, ammonium and phosphate. Product formation is induced by a stationary phase, and continued within a phosphate limited growth phase by feeding glycerol, phosphate and glutamate and/or ammonium with constant feed rates, or with a varying ammonium addition rate when it is used for pH control. The process can be described well by a stoichiometric model and constant CA production rates for the different metabolic conditions. Only one kinetic function was necessary in the model, i.e., to describe the glutamate uptake rate. The stoichiometric coefficients are estimated from the data and the model parameters are fine-tuned by a genetic algorithm. A fairly simple but accurate model with closed mass balances is obtained.