Enzyme engineering for chiral synthesis
- Post by: wangikar_8khp2z
- 10:59AM Apr 11, 2018
- Comments off
Alcohol dehydrogenase (ADH) catalyzed asymmetric reduction is a powerful approach to synthesize chiral alcohols. Researchers in the lab have developed novel ADH enzymes that are highly active, stable and stereo-selective towards a number of substrates. Further, biotransformation processes have been developed that allow favourable space time yield, solute to solvent ratios and cofactor TTNs (total turnover number).
Figure: The Enantioselective reduction of a ketoester by a novel alcohol dehydrogenase
We have demonstrated this for the conversion of ethyl 3-oxo-4-chlorobutanoate (COBE) to ethyl (S)-3-hydroxyl-4-chlorobutanoate [(S)-CHBE], an intermediate in the production of Atorvastatin. Our enzyme engineering efforts include both rational approaches as well as empirical approaches such as directed evolution.
Broader Impact- Alcohol is a common functional group in organic chemistry, either as a constituent of the final product or as a ‘’handle’’ for further synthetic transformation. Chiral alcohols play an important role as intermediates in the synthesis of high value products of pharmaceutical importance. The lab has developed biotransformation processes that meet the following performance criteria: (i) space time yield of > 25 gm/L/hr, (ii) enantiomeric excess (EE) of >99%, (iii) solute to solvent ratio of >1/10 and (iv) cofactor TTN of >5 X 105. Current work includes biotransformation processes for intermediates in cholesterol lowering agents (Atorvastatin, Rusovastatin) and anti-depressants (Bispirone, sertralin