Abstract
This project aims to use ene-reductase [ER] enzymes as a sustainable biotechnology-based approach to produce enantioenriched compounds containing C-F bonds. The fluorine atom can block metabolism sites and affect the molecular shape of bioactive compounds through conformational interactions of the polar C-F bond and so are of significant interest in pharmaceutical applications. We will establish the scope of the bioreduction of activated fluoroalkenes and thus discover efficient enzyme-based systems to produce this important class of compounds. This strategy will provide a new and scalable route to enantioenriched fluoroalkanes and by building multienzyme cascades will generate compounds including chiral fluoroamines and fluoroalcohols.
References
1. D. Karrer, M. Gand, M. Ruhl, ‘Expanding the biocatalytic toolbox with a new type of ene/yne reductase from Cyclocybe aegerita’, ChemCatChem, 2021, 13, 2191-2199.
2. S. Velikogne, W. B. Breukelaar, F. Hamm, R. A. Glabonjat, W. Kroutil, ‘C=C-Ene -reductases reduce the C=N bond of oximes’, ACS Catal., 2020, 10, 13377-13382.
3. D. Dobrijevic, L. Benhamou, A. E. Aliev, N. Dawson, D. Baud, D. Méndez Sánchez, N. Tappertzhofen, T. S. Moody, C. A. Orengo, H. C. Hailes, J. M. Ward, ‘Ene-reductases from a drain metagenome for the selective bioreduction of bicyclic enones’, RSC Adv., 2019, 9, 36608-36614
4. F. Subrizi, L. Benhamou, J. M. Ward, T. D. Sheppard, H. C. Hailes, ‘Aminopolyols from carbohydrates: amination of sugars and sugar-derived tetrahydrofurans with transaminases’, Angew. Chem., Int. Ed., 2019, 58, 3854-3858
5. L. Leipold, D. Dobrijevic, J. W. E. Jeffries, M. Bawn, T. S. Moody, J. M. Ward, H. C. Hailes, ‘The identification and use of robust transaminases from a domestic drain metagenome’, Green Chem., 2019, 21, 75-86.