Bioreactor systems for the production of optically active amino acids and alcohols

Industrial enzyme catalytic reactions for the production of useful optically active compounds have been developed. The first example is a unique process for the production of D-phydroxyphenylglycine ( D- HPG) from D,L-5-p-hydroxyphenylhydantoin. This process involves two immobilized enzyme processes, hydantoinase and N-carbamoyl- D- amino acid amidohydrolase (DCase). A thermophilic bacterium producing thermostable hydantoinase and a mesophilic bacterium producing DCase were isolated, and the thermostability of the latter enzyme was improved by a protein-engineering technique. Both enzymes could be reused in long-term repeated batch reactions as immobilized enzymes for industrial production. The second example is an enzymatic reduction system for the production of optically active alcohols from the corresponding carbonyl compounds. Effective production of ethyl (S)-4-chloro-3-hydroxybutyrate was achieved with high productivity (350 g/L, > 99% ee) by constructing the recombinant Escherichia coli overproducing both carbonyl reductase (S1) and the cofactor-regenerating enzyme, glucose dehydrogenase. We also found various types of reducing enzyme that are useful for the production of various compounds.