Jack Liang, J. Lalonde, B. Borup
Jan 15, 2010
Citations
3
Influential Citations
172
Citations
Quality indicators
Journal
Organic Process Research & Development
Abstract
A KetoREDuctase (KRED) engineered via directed evolution technologies catalyzed the asymmetric reduction of (E)-methyl 2-(3-(3-(2-(7-chloroquinolin-2-yl)vinyl)phenyl)-3-oxopropyl)benzoate to the corresponding (S)-alcohol, a key intermediate in the synthesis of montelukast sodium (Singulair). Through synergistic efforts in process chemistry, molecular biology, bioinformatics and high throughput screening, a KRED with very high enantioselectivity (>99.9% ee) was developed for an economical and simple process that takes advantage of the physical properties of the substrate and product. The evolved KRED is an efficient and robust enzyme for catalyzing the reaction of an essentially water insoluble substrate (c log P ≈ 7) at a 100 g/L loading in the presence of ∼70% organic solvents at 45 °C. The biocatalytic process currently runs at >200 kg scale.