Integration of engineered enzymes into new synthetic and biosynthetic pathways
Prof Jason Micklefield
Recently we have shown that flavin-dependent halogenase enzymes can be used to regioselectively halogenate a range of non-native aromatic compounds. Through structure-guided mutagenesis we were able to improve the activity and also switch the regioselectivity of halogenases. In addition, we demonstrated how halogenases can be combined with chemocatalysts to afford regioselective and regiodivergent arylation and alkenylation of aromatic scaffolds.1 These one-pot chemobiotransformations combine the power of enzymatic C-H activation with transition metal catalysed cross-coupling chemistry to effect reactions that are not possible using biocatalysts or chemocatalysts alone. This lecture will focus on our efforts to exploit halogenases,1-3 alkyltransferases4,5 and other biocatalysts6 to create new reaction pathways in vitro and in cells.
- J. Latham, H. H. Sharif, J.-M. Henry, B. R. K. Menon, S. A. Shepherd, M. F. Greaney, J. Micklefield. Nature Commun. 2016, 7, 11873
- B. R. K. Menon, E. Brandenburger, H. H. Sharif, U. Klemstein, M. F. Greaney, J. Micklefield Angew. Chem. Int. Ed. 2017, 56, 11841–11845
- J. Latham, E. Brandenburger, S. A. Shepherd, B. R. K. Menon, J. Micklefield Chem. Rev 2018, 118, 232-269
- A.-W. Struck, M. R. Bennett, S. A. Shepherd, B. J. C. Law, Y. Zhou, L. S. Wong, J. Micklefield J. Am. Chem. Soc. 2016 138, 3038–3045
- B. J. C. Law, M. R. Bennett, M. L. Thompson, C. Levy, S. A. Shepherd, D. Leys, J. Micklefield Angew. Chem. Int. Ed. 2016 55, 2683–2687.
- D. Francis, M. Winn, J. Latham, M. F. Greaney, J. Micklefield ChemBioChem 2017, 18, 382–386