Optically pure secondary alcohols are valuable intermediates required for the introduction of chiral centres in drugs and agricultural chemicals. These compounds may be prepared through the reduction of the corresponding ketone. The use of enzymatically catalysed reduction of ketones, using ketoreductases (KREDs), has recently started playing an increasingly important role in the industrial-scale production of these compounds. Biocatalysts avoid the use of expensive stoichiometric amounts of chiral reducing agents and permit environmentally friendly, mild processes with less solvents and waste and a lower energy input. To meet the demands of a commercial viability, industry typically formulates strict fitness functions to which the enzyme must adhere. Typically, this would include a desired space-time yield with a minimum enantiomeric excess1. Although limited advances in protein engineering and directed evolution in have helped to improve biocatalysts, a remaining challenge is the matching of selection conditions to the reaction conditions of final industrial application. This project will have a high Scientific Impact on Biotechnology as it introduces a fundamentally new methodology for the development of biocatalysts. Also, comparatively little research has been done in the past on flow processes and directed evolution, a shortcoming this project seeks to address. The outcome of this project will be a high value procedure for converting promising but immature enzymatic processes to fully fledged industrial ones. This project will make a significant contribution to strengthening the European Green Chemistry sector, making this project timely, as the European Chemistry Sector faces the challenges of increased regulation and competition from the USA and BRIC nations. The process improvements stemming from this proposal in the synthesis of pharmaceutical compounds could significantly reduce their cost, impacting the lives of millions of European citizens.
