Asymmetric reduction of α, β-unsaturated ketone to (R) allylic alcohol byCandida chilensis

• DOI: 10.1002/bit.20751
• Publication Date: 2006-01-05T00:46:53Z
• Authors: D.J. Pollard; K. Telari; J. Lane; G. Humphrey; C. McWilliams; S. Nidositko; P. Salmon; J. Moore
• Keywords: Allylic alcohol

A pilot scale whole cell process was developed for the enantioselective 1,2-reduction of prochiral alpha,beta-unsaturated ketone to (R) allylic alcohol using Candida chilensis. Initial development showed high enantiomeric excess (EE > 95%) but low product yield (10%). Process development, a combination statistically designed screening and optimization experiments, improved desired 90%. The fermentation growth stage, particularly medium composition pH, had significant impact on bioconversion while characterization identified diverse challenges including presence multiple enzymes, substrate/product toxicity, biphasic cellular morphology. Manipulating media allowed control morphology predominantly unicellular broth, away from viscous pseudohyphae, which were detrimental bioconversion. activity competing enzyme, produced undesired saturated alcohol, minimized < or =5% by controlling reaction temperature, substrate concentration, biomass level. Despite toxicity effects limiting volumetric productivity, reproducible scaleable demonstrated at with enantioselectivity overall greater than 80%. This preferred route compared partially purified ultra centrifugation, led productivity reduced (g/day). approach proved be valuable alternative chemical reduction routes, as an intermediate step asymmetric synthesis integrin receptor antagonist inhibition bone resorption treatment osteoporosis.