Network in Biocatalyst Discovery, Development and Scale-Up

Industrial biotechnology has the potential to transform the chemical industry by creating more eco-efficient manufacturing processes using natural enzymes (biocatalysts) to reduce greenhouse gas emissions, energy consumption and toxic waste products. Currently many of the day-to-day household products that we rely on, including plastics, pharmaceuticals, agrochemicals, polymers and cosmetic ingredients, are derived from oil-based feedstocks. Competition for oil is intense, with more than 80% being used for generation of energy and as a transportation fuel. Moreover, global supplies are dwindling and hence there is a need to generate an alternative bio-economy based on renewable and sustainable feedstocks. Such feedstocks need to be processed and upgraded in order to provide the broad range of chemicals that are currently manufactured from oil based resources. Biocatalysts offer an attractive approach and indeed are currently used in some cases on large scale for production of specific chemical products. However, over the next 10-20 years it will be necessary to implement this technology more broadly in the chemical industry.

This Network in Biocatalyst Discovery, Development and Scale-Up will help to shape the future of Industrial Biotechnology in the UK by addressing some of the key challenges that lie ahead. The Network will bring together research expertise from the academic and industrial sectors, along with those involved in supply-chains and also the manufacturers and end-users to address these opportunities. Access to biocatalysts developed by academic laboratories, together with the ability of industry to identify, screen and scale-up production of a broad range of biocatalysts, have been identified as major barriers to entry for those in the scientific community wishing to use biocatalysis and Industrial Biotechnology for the development of sustainable processes for the production of high value chemicals. By identifying priority areas, promoting collaboration, sharing best practice, and undertaking proof of concept studies, the Network will seek to develop new biocatalytic process that exploit industrial biotechnology.

This Network will also promote and develop the reputation of the UK internationally and reinforce links with other world leaders in IB excellence. We shall engage with other Centres of Excellence in Europe, USA, Asia and beyond to provide examples of best practice, particularly involving BBSRC sponsored research. As well as providing access to the established expertise of the UK biocatalysis community, the Network will provide the skills base to tackle future barriers to the uptake of biocatalytic processes by helping to train and support the next generation of IB scientists. Training of young scientists is seen as a vital component of the greater uptake of biotechnology.

Finally the Network will also engage in a broad range of dissemination and outreach events in order to educate the wider community as to the benefits of industrial biotechnology and the potential impact that it can have on peoples lives. In addition to addressing scientific and technological challenges, the Network will give due consideration to environmental, social economic and policy related issues that are important as we transition from an oil-based economy to one based on renewable feedstocks.

Access to a broad range of biocatalysts for R&D is widely recognised as rate limiting in the uptake of IB, particularly by the chemical industry where there is desire to replace existing processes with those based upon sustainable feedstocks and catalysts. The Network will provide significant long-term benefits to a substantial percentage of the IB community: seeking to discover, develop and make available a broader range of biocatalysts which can be screened and applied by the end-users.
(i) Biocatalyst discovery and screening: New enzymes will come from sequenced genomes and metagenomics (with next generation sequencing) which allows access to enzymes from non-culturable organisms. This will allow expression and screening using high-throughput methods of thousands of new biocatalysts. (ii) Biocatalyst development and optimisation: Robust hosts that can withstand high concentrations of organic compounds and hosts to plug in new enzymes/multienzyme pathways are needed. We will use synthetic biology concepts and methods to build new pathways. Individual enzymes will be engineered towards the characteristics required for practical application, e.g. stability, selectivity and broad substrate coverage, compatibility with chemical catalysts and solvents, helping to integrate enzymes into more chemical processes. Biocatalyst fusions will be explored to link pairs of enzymes for sequential steps in an enzyme cascade. (iii) Biocatalyst scale-up: The industrial partners will develop the fermentation processes to produce the enzymes whilst ensuring the enzymes are developed so that they can be efficiently/stably produced at scale for global supply.
Major advances in all of these areas will be required to develop a much broader range of stable biocatalysts which are suitable for screening by end-users - close collaboration is required between academia and industry who can all contribute to the overall goal of a larger toolbox of biocatalysts for practical application.

This Network will generate a critical mass of academics, industrialists and policy makers who will work together to bring about a step changes in the development of sustainable processes for the production of high value chemicals through the greater utilisation of IB. These changes will benefit provide wider environmental benefits through the replacement of limited, petrochemically derived chemicals / materials / resources with renewable environmentally benign reagents, catalyststs and processes.

For example, the proof-of-concept studies will ultimately lead to more competitive, collaborative, cross-disciplinary and integrative research proposals. The Network is targeting over 3-5 years the following; two sLoLa grants (£5M each), 5 ERA-NET grants (£10M), 5 Horizon 2020 grants (£40M), IB Catalyst funding (£5M) with a predicted 10-fold return on investment, significantly enhancing the UK R&D portfolio in this area. Interaction between the academic research base and technology-deploying, associated value-chain and end-user businesses will fast track the translation of research activities within the PoC programme and wider Network, thus enhancing the rate at which new research discoveries are brought to market and in turn increasing the value to the UK economy.

The Network will raise the profile of IBBE within the UK, EU and beyond by; i) attending high profile international research conferences, ii) invitation of key worldwide representatives from across academia, industry and policy makers to attend Network events, iii) exchange of scientists at all levels from postgraduate to principal investigators, iv) contribution to EU Horizon 2020 future calls for proposals in Industrial Biotechnology. The Network, in collaboration with business, will provide the leadership via Network sandpit events and the proof-of-concept projects, to develop the challenges to be addressed by the IB Catalyst fund. The early stage researchers involved in this Network will benefit from broad training in this highly desirable research field. The skills gained will help to produce 'rounded' scientists with a skill set that is attractive to companies wishing to engage in biocatalysts discovery, development, and scale-up, thus improving their employability. These individuals will then be able to make a practical and valuable contribution to the continued growth of this type of research activity in the UK.

The Network will build upon an assortment of established collaborations. Professors Turner and Ward already have a significant research portfolio within the field of IB. Both have an international presence in the scientific remit of the Network and significant funding/experience of managing existing collaborative Centres of Excellence in Biocatalysis. NJT is the Director of CoEBio3 which has a strong network of Industrial Affiliates, now entering the its third Phase (Phase I (2005-2010), Phase II (2009-2012), Phase III (2013-). CoEBio3 coordinate a series of EU FP7 funded projects; CHEM21, BIONEXGEN, AMBIOCAS, Marie Curie Initial Training Network (BIOTRAINS, P4FIFTY). NJT is also PI on BBSRC sLoLa with GSK 2012-2017. JW is PI for the Synbion Synthetic Biology Network, MRes Synthetic Biology training grant, BBSRC, EPSRC, Wellcome, Leverhulme and MRC grants; and is the lead in new biocatalyst discovery in BiCE (Biocatalysis Chemistry Engineering Interface programme). The collaborations listed above will serve as a basis for the Network and participation in meetings associated with each project will act as a vital mechanism for building a pan-European Network of scientists and industrialists who share a common interest in Industrial Biotechnology.