The overall aim of WP3 is to develop a range of engineered biocatalysts for application in the synthesis of pharmaceutical building blocks and APIs. Within WP3 we have specifically targeted classes of biocatalyst (e.g. C-C bond formation; redox reactions; oxidation of alkenes) that catalyse reactions of interest to the pharmaceutical industry and where the existing chemical methods are perceived to be either in need of replacement and improvement by the introduction of biocatalytic alternatives. Novel biocatalysts are identified via a number of different approaches (e.g. bioinformatics, metagenomics screening, published sequences) and then subsequently engineered in order to improve a range of characteristics including substrate tolerance, stereoselectivity, stability and process compatibility. We also demonstrate the application of these new biocatalysts in synthesis, particularly by developing new synthetic routes to target molecules based upon applying the principles of ‘biocatalytic retrosynthesis’. Novel panels of biocatalysts are transferred to EFPIA members for in-house evaluation in order to identify specific areas where they might be applied for target molecule synthesis. EFPIA members are also actively involved in characterising these biocatalysts and suggesting areas where further development should be focussed in order to expand the potential application of the panels.

Specific projects that are currently underway in WP3 include:

  • Scaleable amide synthesis from esters and amines.

  • Panels of biocatalysts available for a broad range of redox reactions.

  • Haloalkane dehalogenases and cyclases for alcohol activation.

  • Aldolases as catalysts for stereo controlled synthesis of fluorinated targets.

  • Metal-dependent enzymes for asymmetric dihydroxylation.

  • New scaleable multi-component reactions involving bio- and chemo-catalysis.

  • Biocatalytic processes in neoteric (e.g. solvents from biomass, scCO2) solvents.

  • Applications of scCO2 in biotransformations involving amines.

  • Threonine aldolases for asymmetric synthesis of products containing quaternary centres.

In order to develop these engineered biocatalysts we are employing a range of different technologies in parallel including protein engineering (rational and directed evolution), reaction engineering (e.g. bio-based solvents), enzyme immobilisation (whole-cell or lyophilised enzyme) and process engineering (e.g. flow or use of scCO2). The overall aim of WP3 is to significantly expand the toolbox of available biocatalysts for the synthetic chemist. To this end we are also running training programmes in order to encourage the uptake and adoption of biocatalysis in both medicinal and process chemistry within the pharmaceutical industry.