About the Project
This PhD project involves the rational design, preparation and assessment of artificial metalloenzymes. Nature’s catalysts, enzymes, have been perfected by evolution to perform reactions under mild conditions and with enviable asymmetric control and selectivity. However, the active sites of metalloenzymes are primarily restricted to first row transition metals, despite catalysis with heavier transition metals offering more diversity in terms of reactivity. This is primarily due to these heavier metals not being “biologically available”. This PhD project will combine the advantages afforded by both the xenobiotic and the enzymatic catalytic worlds, so as to create new biotechnology for the efficient and catalytic synthesis of complex molecules.
Xenobiotic catalytic sites will be engineered into increasingly complex and structured peptide and protein assemblies. This includes, but is not limited to de novo designed miniature artificial protein scaffolds, specifically coiled coils. The resulting artificial metalloenzymes with xenobiotic active sites will be screened for asymmetric catalysis, and used to establish key structure-function relationships. This is a multidisciplinary project incorporating elements of transition metal and asymmetric catalysis and synthetic biology.
This project is collaborative between the Peacock and Davies groups in the School of Chemistry. Candidates should have an interest in structure and function, multi-step synthesis, method development and transition metal catalysis.
This is part of the Midlands Integrative Biosciences Training Partnership. See for details of how to apply
http://www2.warwick.ac.uk/fac/cross_fac/mibtp/pgstudy/phd_opportunities/
Funding Notes
This is part of the Midlands Integrative Biosciences Training Partnership; please check this website for details of how to apply and deadlines:
http://www2.warwick.ac.uk/fac/cross_fac/mibtp/pgstudy/phd_opportunities/
Please contact either Dr Paul Davies or Dr Anna Peacock for more information:
Telephone +44 (0) 121 414 4408; Email [Email Address Removed]
Telephone +44 (0) 121 414 4362; Email [Email Address Removed]
Websites: http://chemweb.bham.ac.uk/~peacoafa/Peacock_Website.htm
https://www.birmingham.ac.uk/research/activity/chemistry/Davies/index.aspx
References
[1] Peacock, A. F. A.; Bullen, G. A.; Gethings, L.; Williams, J. P.; Kriel, F. H.; Coates, J. “Gold-Phosphine Binding to De Novo Designed Coiled Coil Peptides”, J. Inorg. Biochem., 2012, 117, 298.
[2] Adcock, H. V.; Chatzopoulou, E.; Davies, P. W. “Divergent C-H Insertion-Cyclization Cascades of N-Allyl Ynamides” Angew. Chem. Int. Ed. 2015, 54, 15525.
[3] Berwick, M. R.; Lewis, D. J.; Pikramenou, Z.; Jones, A. W.; Cooper, H. J.; Wilkie, J.; Britton, M. M.; Peacock, A. F. A. “De Novo Design of Ln(III) Coiled Coils for Imaging Applications” J. Am. Chem. Soc., 2014, 136, 1166.
[4] Zastrow, M.; Peacock, A. F. A.; Stuckey, J.; Pecoraro, V. L. “Hydrolytic Catalysis and Structural Stabilization in a Designed Metalloprotein” Nature Chem., 2012, 4, 118.