DEVELOPMENT OF A RECOVERY AND RECYCLE PROCESS FOR A PSEUDOMONAS LIPASE USED FOR LARGE-SCALE ENZYMATIC-SYNTHESIS

Enzymes are potential catalysts for a wide range of large-scale chemic al synthesis steps, particularly when the creation of a specific chira l center is desired. The efficient recycling of the enzyme catalyst an d the removal of carryover impurities were crucial factors in the impr ovement of a stereoselective ester hydrolysis step used in the synthes is of a selective leukotriene antagonist. In this enzymatic reaction s tep, the substrate and product were both largely insoluble, while the enzyme was soluble in the aqueous reaction mixture. Microfiltration an d ultrafiltration of the slurry reaction mother liquor indicated near 100% enzyme protein recovery, while activity recovery was about 70% to 80%. These activity losses might be accounted for by enzyme degradati on (1 to 2 mg/L . h) during the 40-hour reaction period. Dissolved imp urities, principally a diacid byproduct, in the enzyme recycling strea m were reduced 60% to 70% by either lowering the solution pH to 4.0 or raising the solution ionic strength to 1 M. (C) 1993 John Wiley & Son s, Inc.