Biocatalysis, chemocatalysis, enzyme kits, chiral, fermentation, molecular biology, purification, route selection

Process Development

There is a common misconception that enzymes are unstable and expensive, work only under high dilution, and do not lend themselves well to economical scaleable chemical processing. This perception has discouraged many chemists from working with enzymes.

This is far from the reality, and there are ever-increasing numbers of biotransformations being performed at multi-tonne manufacturing scale, where biocatalysis has provided the most efficient processing solution. In addition, the timelines to develop these bioprocesses are now comparable with chemistry scale-up, due to the availability of “Off-the-Shelf” enzymes such as Almac’s selectAZymeTM platform as highlighted below:

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Process Development Process Flow

It is not uncommon for an enzyme to contribute as little as $1-10/kg product in cost, and to transform a substrate at 200 g/L in the biotransformation step. In some cases no solvent is needed, and substrates can simply be mixed with the enzyme to give the product.

As energy costs and environmental issues increase the need for the chemical industry to reduce costs and waste, green and renewable bioprocesses are coming to the rescue.

There are a number of key factors involved in the development of a biocatalytic process including substrate concentration, enzyme loading, solvent choice, product extraction and isolation. Investigation of these factors can utilise what is already known in the literature and patents, and through Almac’s expertise in biocatalysis process development, which includes the separation of enantiomers derived from kinetic bioresolutions as well as asymmetric synthesis. These bioprocesses have been carried out at multi-kilogram scale. Development work consists of investigating reaction robustness by stress testing each of the relevant parameters, taking the reaction to its limits and then setting the optimised conditions. Almac has carried out bioprocesses to GMP standard in its manufacturing plant.

Due to the efficiency and ease of use of biocatalysts, Almac has developed novel routes to chiral intermediates from mg scale up to 100′s of kilos.

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