We target enzymes and 'tailor' their reactivity for use in biocatalytic processes, chemicals synthesis and biofuels projects. We use a variety of engineering methods to manipulate specificity and improve biocatalytic performance. Both structure-based engineering and directed evolution methods are used, employing where possible automated/robotics platforms for high throughput.
We currently use both natural and engineered biocatalysts in pathway assembly/refactoring to generate prototype strains for applications in chemicals biosynthesis and biofuels programmes. Our work on biocatalyst and pathway engineering is then integrated into wider consortium-based programmes involving expertise in systems biology, metabolic regulation, chassis engineering and process optimisation. Our core programmes therefore provide novel components in synthetic biology and assemble these building blocks/modules, pathways and regulatory components. This requires development of new platform technologies to accelerate the (re-)design of building blocks and pathways, through exploitation of knowledge of the structures and mechanisms of enzyme catalysts.
Some Recent Biocatalyst Engineering Publications:
A biocatalytic method for the chemoselective aerobic oxidation of aldehydes to carboxylic acids (2018) T. Knaus, V. Tseliou, L.D. Humphreys N. S. Scrutton, F. G. Mutti. Green Chemistry 20, 3931-3943, DOI: 10/1039/C8GC01381K Featured on front cover
Experiment and simulation reveal how mutations in functional plasticity regions guide plant monoterpene synthase product outcome (2018) N.G.H. Leferink, K.E. Ranaghan, V. Karuppiah, A. Currin, M.W. van der Kamp, A.J. Mulholland, N.S. Scrutton, ACS Catalysis 8, 3780-3791, DOI: 10.1021/acscatal.8b00692
Discovery, characterisation, engineering and applications of ene reductases for industrial biocatalysis (2018) H.S. Toogood, N. S. Scrutton, ACS Catalysis, 8, 3532-3549 DOI: 10.1021/acscatal.8b00624
Engineering the ‘missing link’ in biosynthetic (–)-menthol production: bacterial isopulegone isomerase (2018) A. Currin, M. Dunston, L. Johannissen, K. Hollywood, M. Vinaixa, A. Jervis, N. Swainston, N. Rattray, J. Gardiner, D.B. Kell, E. Takano, H. S. Toogood, N. S. Scrutton, ACS Catalysis, 8, 2012-2020 DOI: 10.1021/acscatal.7b04115
Bio-derived production of cinnamyl alcohol via a three step biocatalytic cascade and metabolic engineering (2018) E. Klumbys, Z. Ziga, N. Weise, N. J. Turner, N. S. Scrutton, Green Chemistry, 20, 658-663 DOI: 10.1039/C7GC03325G
Speeding up enzyme engineering computationally (2017) Scrutton, N. S., IUCrJ 4, 5-6 DOI:10.1107/S2052252516019692