100 years after discovery, DSM offers first industrial production of PharmaPLE

DSM Pharma Chemicals has launched a recombinant pig liver esterase, which enables new opportunities to reduce production costs for pharma intermediates.

Access to recombinant pig liver esterase at any scale, without batch-to-batch variations, and as a non-animal derived form has been a longstanding wish for many chemists. DSM believes it has cracked it with PharmaPLE

Oliver May, DSM's competence manager in biocatalysis, said: 'We are very pleased to have proven the real benefit of PharmaPLE by replacing a classical resolution process with a more economic and greener enzymatic manufacturing process for a key intermediate of a recently launched hypertension drug.'

More than 100 years ago, it was discovered that an enzyme extract from pig liver is able to hydrolyze racemic esters of mandelic acid into optically active carboxylic acids. Now pig liver esterase is known to be one of the most versatile biocatalyst for organic chemists. It out competes many of the large number of commercially available esterases in terms of a broad substrate spectrum and excellent enantio- and regio-selectivity. However, it is animal derived, varies significantly in quality from batch to batch and is therefore not suitable for pharma applications.

DSM's collaboration partner, Prof. Schwab from the Graz University of Technology (Austria), has identified the most useful isoform of PLE, the PharmaPLE. Based on DSM's capabilities in enzyme development and enzyme production, a highly efficient and patented microbial expression system and fermentation process was developed, which is now running at 25.000 liter scale. This makes PharmaPLE available at unlimited scale, in an unlimited form (reproducible, safe, non-animal derived kosher and halal) and therefore offers unlimited opportunities for pharma applications to our customers.