Biocatalysis has an increasing role in replacing heritage chemistry and enabling more efficient routes to target compounds. Modern biotechnology and enzyme engineering allow unprecedented access to improved and novel biocatalytic routes. Biocatalysis can be used to manufacture target compounds via a more cost-efficient and sustainable route or enable diversity in chemical diversity programmes, e.g. via late-stage functionalisation.
Isomerase provides biocatalysis services to a wide range of sectors and can act as an innovation partner from concept to manufactured biocatalytic products.
Isomerase has expertise not only in discovering and engineering new enzyme biocatalysts for biocatalytic routes but also in developing high-titre scalable manufacturing processes for enzyme production.
Example projects in biocatalysis
Example biocatalysis projects include:
- Enzyme identification - following phenotypic or literature evidence of target activity in a microbial strain, we have sourced strains and generated protocols for the growth and preparation of genomic DNA. We then completed genome sequencing and analysis to generate a shortlist of candidate enzymes which were expressed and tested to confirm the target activity
- Enzyme expression - we have worked across multiple microbial expression hosts, e.g. Escherichia, Pichia (Komagataella), Bacillus and various actinomycetes, to ensure expression systems that are not only best suited for the enzyme of interest but also the eventual commercial process
- Enzyme engineering and evolution - we have engineered enzymes using designed synthetic DNA arrays to allow screening to identify candidates with the desired properties
- Enzyme USP/DSP development - from fermentation to cell disruption (e.g. chemical lysis, sonication, homogenisation) and purification (TFF – tangential flow filtration, affinity purification, ÄKTA column purification, inclusion body isolation, stabilising agents), we have developed processes to either rapidly access semi-purified enzymes for initial trials or enable scaled enzyme manufacture
- Reaction and Process optimization - we can apply in-house methods or develop and optimise bespoke methods depending on the client’s needs. We offer a range of proven industrial approaches to develop analytical methods and use tests for biocatalytic routes which can be used to carry out initial optimisation of typical parameters (enzyme loading, pH, buffer, excipients etc.) before optimising reaction workup
- Tech transfer - we are skilled at generating process documentation and have supported the transfer of processes to outsourced facilities at pilot and manufacturing scales. Support is tailored to each client’s needs and can be limited to documentation preparation only, but more typically includes help with the selection and assessment of scale-up facilities
- Enzyme supply - we have the capacity to generate gram quantities of enzyme in-house using scalable USP/DSP methods. For larger quantities, we collaborate with a network of scale-up CDMO partners where we can manage the tech transfer process and manufacturing campaigns.
- Compound supply – we can generate diverse sets of compounds via biocatalytic transformations. The resultant small molecule can be the starting point for e.g. lead optimisation studies in drug discovery
How can biocatalysis improve pharmaceutical manufacturing processes?
Biocatalysts offer a number of potential improvements over traditional chemical catalysis including:
Enhanced regio- and stereo-selectivity – Enzymes can be highly selective catalysts, producing specific products from a mixture of reactants with minimal side products. They can, for example, perform chiral transformations or resolve racemic mixtures. This can improve the quality of a final API and support CMC.
Efficiency – Enzymes can be very efficient catalysts, accelerating reactions by orders of magnitude. This can lead to a reduction in reaction times or costs of a reaction step. Single enzymes can also combine multiple chemical synthesis steps into a single biocatalytic step, or be utilised in a cascade (in tandem with other biocatalysts) to effect a multistep transformation in a single pot vessel
Sustainability – Biocatalytic reactions are typically carried out using mild aqueous conditions, using water as the major solvent. This can reduce the levels of potentially hazardous, expensive and fossil fuel-dependent solvents required for an API manufacturing process. The lower temperatures often required can reduce the energy required for a synthesis.
Contact us for more information on our biocatalysis services or to request a quote for your biocatalytic project.