The team at Isomerase have carried out numerous projects developing novel biocatalytic routes to products. Examples include:
Enzyme identification – Following phenotypic or literature evidence of target activity in a microbial strain, we have sourced microbial strains and generated protocols for 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. These hits can then be improved by a campaign of process optimisation – see below.
Enzyme expression – We work across multiple microbial expression hosts, e.g. E. coli, Pichia (Komagataella), Bacillus, various actinomycetes, to ensure an expression system that is not only best suited for the enzyme of interest but also the eventual commercial process.
Enzyme engineering and evolution – our synthetic biology team is able to manipulate genes coding for enzymes using various approaches. For example, we can target specific amino acids based on literature evidence or enzyme modelling, or by using designed DNA arrays to generate a mixture of variants that can be rapidly expressed and screened 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, column purification, inclusion body isolation, stabilising agents), we offer a range of robust and scalable methods to either rapidly access semi-purified enzymes for initial trials through to techno-economically attractive processes for scaled enzyme production.
Process optimisation – We can apply our highly productive in-house processing methods or, if required, develop and optimise bespoke methods depending on the clients 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 (pH, buffer, excipients etc.).
Tech transfer – we are skilled at generating process documentation and supporting 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 and providing experienced technical staff on site to oversee batches and ensure a successful campaign.
Enzyme supply – We have capacity to generate gram quantities of enzyme in-house for initial trials 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.