Joe Adams – GlaxoSmithKline
What is your background and current job role?
I am based within GlaxoSmithKline as part of the R&D organisation, specifically the AC (Active Pharmaceutical Ingredient Chemistry) department as a team manager supporting synthetic biochemistry. The team is focused on using biotechnology to develop improved (more sustainable, faster, shorter, cheaper) routes to small molecule manufacture. Much of our work is focused around biocatalysis but we also do some fermentations to natural products and are increasingly considering synthetic biology approaches.
My background has chemistry at its core with a PhD in organic chemistry followed by a couple of post docs with more of an emphasis on biocatalysis. I joined GSK in 1994 and have remained with the company ever since in various roles. In the last decade I have been much more involved in biotechnology as I sought to grow a team in the UK capable of taking advantage of the many advances in biology to improve our synthetic approaches. This team is now part of a global initiative, focused predominantly in the UK and US, and includes multiple different disciplines (e.g. biochemistry, bioinformatics, computational sciences, chemistry, enzymology, enzyme engineering, fermentation, molecular biology…..) from different departments within the organisation.
What Industrial Biotechnology and Bioenergy (IBBE) related project is currently being undertaken by your organisation?
We undertake a large number of different IBBE related projects. GSKs largest volume drug is the antibiotic amoxicillin with annual manufacturing volume approaching 3000 tonnes. Most of our projects are much smaller than this and would typically involved using a well developed class of enzymes (eg ketoreductases or transaminases) in one stage of a chemical process. We have had success with many different classes of enzymes such as enoate reductases, epoxide hydrolases and monooxygenases – none of which is particularly well developed today. To cater for the varied nature of the projects, and to develop new tools for the future, means we have adopted an open innovation approach to our R&D and have many partners both in industry and academia. Our largest single collaboration would be with Codexis to bring their enzyme evolution technology into GSK and apply it to our projects. We have many links through to academia in the UK from simple CASE awards to large multi-partner collaborations (eg CoEBio3, IBioIC, different NIBBS or the Innovative Medicines Initiative collaboration CHEM21).
What do you think the challenges related to this project are in the next 1-5 years?
There are multiple challenges!
1. More classes of different, developed enzyme panels across a greater range of substrate chemical space so that promising hits can be quickly identified.
2. Improved (automated?) approaches for the screening of enzymes against the desired transformation.
3. Even with a comprehensive set of tools to enable enzyme evolution it still typically takes months to go from a hit to get the desired protein with the desired properties (activity, stability, stereoselectivity etc) suitable for full manufacture. This is often not a good fit for project timelines. It’s a commitment. Ideally we would wish for this process to be much faster, more of an experiment.
4. More productive processes for enzyme production. Greater expression levels, higher ODs, improved production strains, simpler downstream processing.
5. More productive ways to use biocatalysts (eg continuous / flow approaches, membrane technologies).
6. Improved methods (in silico, in vitro and in vivo) for the application of synthetic biology to develop new ‘cell factory’ approaches, using human-designed biochemical pathways, to starting materials, intermediates or APIs at concentrations that could be adopted by industry.
How can other CBMNet members help you and your organisation with your research?
As a global pharma company GSK have a broad range of projects and subsequently a wide interest in new methodologies or the novel application of older methodologies. We are constantly seeking better ways to conduct our R&D and networking across partners with aligned interests from both academia and industry is a key component of this.