The L-tert-leucine synthesis was performed continuously in series of two enzyme-membrane reactors by reductive amination of trimethylpyruvate with leucine dehydrogenase. The necessary "native" cofactor NADH is regenerated with the aid of a second enzyme, formate dehydrogenase.
Considering detailed kinetic studies of initial reaction rates under conditions relevant to the process a kinetic model was developed. The model shows that the overall reaction rate is strongly inhibited by the reaction product. The reactor's models combine the mass balances and proposed kinetic equations. The model adequacy was verified by using it to simulate the experiments and by comparing experimental and computed conversion, space-time yield and enzyme consumption.
The calculations for the three reactor's types (batch, single CSTR and a cascade of two CSTRs in series) were compared. The results showed that a single CSTR is no favourable reactor configuration due to the very strong product inhibition. Space-time yield drops from 560 g litre-~ day-~ in a batch reactor to 110 g litre-~ day-1 in a single CSTR at the highest conversion of 98 %. At the conversion of 95 % the difference in biocatalyst costs between batch and two CSTR in series is negligible. Therefore the use of two enzyme membrane reactors in series was proposed.