Process Development
There is a common misconception that enzymes are unstable, work only under high dilution, expensive, 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 as highlighted below:
It is not uncommon for an enzyme to contribute $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.
The key factors involved in biocatalysis development are: substrate concentration; enzyme loading; acyl donor; solvent choice and product extraction; and isolation. This can utilise what is already known in literature, patents and Almac’s expertise in biocatalysis process development. Almac has expertise in the separation of enantiomers derived from kinetic bioresolutions as well as asymmetric synthesis and have scaled these bioprocesses to multi-Kg. Development work consists of reaction robustness and stress testing of each of the parameters, taking the reaction to its limits and then setting the optimised parameters for the reaction. Almac has carried out bioprocesses to GMP standard in its pilot plant.
Due to the speed and ease of use of biocatalysts, Almac has developed novel routes to chiral intermediates at mg to 100's of grams for small scale supply needs. These novel chiral building blocks can feed directly into drug discovery programs.
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