Genetic Code Expansion in Catalysis

The genetic code has been expanded by redirecting specific codons to encode amino acids beyond the 20 standard amino acids. Current enzyme design and engineering strategies rely predominantly on the twenty natural amino acids, greatly impacting the range of mechanisms that can occur within the active site of an enzyme. Using genetically encoded non-canonical amino acids (ncAAs), biocatalysts can be optimised, improving their stability and activity.
Genetic code expansion is well developed in E. coli with over 200 ncAAs encoded to date, but is underdeveloped in yeast due to the eukaryotic background which provides additional challenges such as problematic release factor competition and poor transcription of many prokaryotic tRNAs. These limitations can be potentially overcome by the development of Sc2.0. The unique synthetic chromosomal rearrangement and modification by loxP-mediated evolution (SCRaMbLE) function built into Sc2.0 can allow insertions, inversions, deletions and translocations of the genomic background to occur, removing features that are detrimental to GCE. Future synthetic yeasts with a greater number of codons available for ncAA encoding will allow a wide-range of non-natural chemistries to be built into protein-based biomaterials, biotherapeutics and catalysts.

iCAT will work with industry partners to create an holistic approach to the training of students in biocatalysis, chemocatalysis, and their process integration. Traditional graduate training typically focuses on one aspect of catalysis and this approach can severely restrict innovation and impact. Advances in technology and fundamental reaction discovery are rendering this silo-approach obsolete, and a new training modality is needed to produce the next generation of chemists and engineers who can operate across a far broader chemical continuum. iCAT will meet this challenge with a state-of-the-art CDT, equipping the next generation of scientists and engineers with the skills needed to develop future catalytic processes and create the functional molecules of tomorrow.

The UK has one of the world's top-performing chemical industries, achieving outstanding levels of growth, exports, productivity and international investment. The UK's chemical industry is a significant provider of jobs and creator of wealth, with a turnover in excess of £50 billion and a contribution of over £15 Billion of value to the UK economy [2015 figures]. iCAT will deliver highly skilled people to lead this industry across its various sectors, achieving impact through the following actions:

1. Equip the next generation of science and engineering leaders with the interdisciplinary skills and knowledge needed to work across the bio and chemo catalytic remit and build the functional molecules we need to structure society.

2. Provide a highly skilled workforce and research base, skilled in the latest methodologies, strategies and techniques of catalysis and engineering that is crucial for the UK's Chemical Industry.

3. Build the critical mass necessary to support effective cohort-based training in a world-class research environment.

4. Develop and disseminate new catalytic technologies and processes that will be taken up by industrial and academic teams around the world.

5. Encourage Industry to promote research challenges within the CDT that are of core relevance to their business.

6. Provide cohesion in the integration of biocatalysis, engineering and chemocatalysis to create a more unified voice for strategic dialogue with industry, funders and policy makers, and more generally outreach and public engagement.

7. Draw-in and bring together Industrial partners to facilitate future Industrial collaborations.

8. Benefit Industrial scientists through interactions with the CDT (e.g. training and supervisory experience, exposure to cutting-edge synthesis and catalysis etc).

9. Link with other activities in the landscape: bringing unique expertise in catalysis to, for example, externally-funded University-led initiatives, EPRSC Grand Challenge Networks, and the National Catalysis Hub.