Enzymatic processes for fine chemicals and pharmaceuticals: Kinetic simulation for optimal R-phenylacetylcarbinol production

Abstract

An optimal feeding strategy with a 1:1.2 molar ratio of benzaldehyde: pyruvate has been developed to maximize the enzymatic production of the pharmaceutical intermediate R-phenylacetylcarbinol (PAC) based on a previously published model for this intermediate. The results of the simulation indicate with pyruvate decarboxylase (PDC) at an initial carboligase activity of 4 U ml-1that up to 730 mM PAC would be produced in 81 h. However, the experimental results show an appreciably lower maximum level of PAC (viz 300 mM) produced after only 54 h, although enzyme activity was maintained at similar or higher values than in the simulation results. It is possible that the increasing PAC concentrations and associated by-products (acetoin and acetaldehyde) have resulted in significant inhibition of PDC during the course of the biotransformation and future model development will need to include one or more product inhibition terms in its structure. © 2006 Elsevier B.V. All rights reserved.