Challenges for Biocatalysis

When considering biotechnology as a solution you fundamentally have two approaches;

(i) change a step in a process or

(ii) rip up the process and start from scratch, as described by Professor Nick Turner (Co-ordinator of the BIONEXGEN Project, University of Manchester) at the event. Nick provided a presentation on Enzymatic Amine Synthesis (which can be downloaded here) and set out more broadly five major considerations in biocatalysis:

• Biocatalysts (enzymes/whole cells) can replace chemo-catalysts in synthetic routes.

• Biocatalysts can also enable new synthetic pathways which may be shorter, more efficient and more sustainable.

• Combining bio/bio- and bio/chemo-catalysis generates opportunities for the design of new synthetic routes.

• Need biocatalysts with broad substrate scope that are active and stable under the conditions of a chemical process (fit biocatalyst to process rather than vice-versa).

• Range of emerging technologies for biocatalyst development (directed evolution/rational engineering/pathway engineering). Using amines as an example, Nick described their versatility and gave examples of their end use; intermediates for pharmaceuticals and agrochemicals, building blocks for polyamides (e.g. diamines), solvents, cleaning agents, wood treatment, personal care, water treatment, lubricants and disinfectants. Traditionally these have been manufactured using chemical processes, e.g. reductive amination, or addition of ammonia to olefins, which often require high temperature, pressure, pH and some form of metal catalyst. Developing novel biocatalysts for amine synthesis bypasses these inherently aggressive conditions.

The BIONEXGEN project has enabled the further development of these types of enzymes including Lipases, Amine Oxidases, Imine reductase, Transaminases and Amine Dehydrogenases for the production of alkaloids and synthetic API’s amongst others. However, there are still numerous challenges and hurdles to be identified and overcome, for example:

• Can we design new and general synthetic routes to target classes (e.g. amino acids, alkaloids, terpenes etc.) based upon bio- and chemo-catalysis?

• Can we develop guidelines for route design for synthetic chemists (biocatalytic retro-synthesis)?

• Where are the gaps in biocatalysis – which reactions are currently not available (and would be desirable)?

• How do we significantly expand the biocatalysis toolbox?

Nick Turner and the University of Manchester will be looking to Horizon 2020 funding opportunities to address these as part of innovative consortia.