Pig liver esterase makes a comeback in biocatalysis

By Huw Kidwell

- Last updated on GMT

Related tags Bovine spongiform encephalopathy

A new recombinant pig liver esterase (PLE) biocatalyst that
sidesteps concerns about the safety of animal-derived versions has
been launched by DSM Pharma Chemicals.

The enzyme PLE is used on a commercial scale as a biocatalyst in the resolution of mixtures of chiral esters by hydrolysis to produce optically active carboxylic acids with excellent enantioselectivity.

It was launched at Informex earlier this month, and has already been used in the synthesis of a starting material for a new hypertension treatment.

DSM's PLE product - called PharmaPLE - has been successfully produced by recombinant techniques from non animal sources in large scale allowing reactions using the enzyme to be carried out at scales of 25,000 litres.

PLE has been shown to be one of the most useful chiral esterases available commercially as it is applicable to such a wide range of materials and can produce superior enantio- and regio-selectivity.

The application of this product will significantly reduce the production costs of chiral starting materials as it can be used in large scale.

Resolution of acids is a well known route for the production of chiral intermediates (acids are good starting materials for further transformation).

Oliver May, DSM's competence manager in biocatalysis commented: "Access to recombinant pig liver esterase at any scale, without batch to batch variations, and as a non-animal derived form was a longstanding wish for many chemists.

Now this wish has come true."

"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."

PLE fell out of favour in the 1990s because of concern over the use of animal derived products in chemical processes in a time of uncertainty about BSE (bovine Spongiform Encephalitis).

DSM Chemicals was able to develop and scale up the new PharmaPLE enzyme during a four month period in 2007.

The project involved the collaboration of six research sites and earned the cross-functional 75 strong DSM team and a team from Graz University of Technology in Austria the company's Gold DSM Innovation Award for 2007.

The methodology has now been refined again to reduce the time taken for production of the enzyme and the cost.

Pharmaceutical chemists now have an excellent tool at their disposal for the production of chiral intermediates on a large scale.

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