Chiral alcohols, usually secondary alcohols, play an important role as intermediates in high value products of pharmaceutical importance. Among the various enzymatic routes available for chirally selective synthesis of secondary alcohols, that involving oxidoreductase catalyzed asymmetric reductions is a particularly powerful approach as it potentially allows 100% of the starting material to be transformed into the desired enantiomer.
In this network project involving a multi-disciplinary team and an industry partner, we have chosen to work on microbial oxidoreductases. This is a class of enzymes with potential in chiral synthesis of commercially important secondary alcohols. Several proof of concept studies have been reported on this enzyme although the following challenges remain to be addressed. (i) High cost of enzymes, (ii) Substrate specificity and stereo-selectivity of enzyme: The wild-type enzyme may not have high activity or stereo-selectivity for the chosen substrate, (iii) Industrial applications require solute to solvent ratio to be no more than 1:10 while literature reports work in the range of 1:100. (iv) Recycling of the enzyme and co-factors. A successful commercial application therefore will require an enzyme that is highly active and stereoselective towards the substrate of choice, tolerates high substrate concentrations, stable and amenable to recycling and is affordable. The student will have an opportunity to work on the following objectives:
1. Improvement of the desired properties of oxidoreductase enzymes via directed evolution.
2. Development of cofactor recycling system with formate dehydroganase and by using a membrane reactor.