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Gold coiled coils for use as artificial metalloenzymes - Designing new ligands for asymmetric synthesis

Principal Supervisor: Dr Anna Peacock - School of Chemistry

Co-supervisor: Paul Davies

PhD project title: Gold coiled coils for use as artificial metalloenzymes - Designing new ligands for asymmetric synthesis

University of Registration: University of Birmingham

Project outline:

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. Chemical catalysts, on the other hand, offer more diversity in terms of reactivity, albeit their simpler design means that reaction outcomes are more difficult to control. This PhD project will combine the advantages afforded by both the chemical and the enzymatic catalytic worlds toward creating new biotechnology for efficient synthesis of complex molecules. Chemical catalytic sites, inspired by small molecule gold catalysts, will be engineered into de novo designed miniature artificial protein scaffolds, specifically coiled coils (see Figure). The resulting artificial metalloenzymes will be screened for asymmetric catalysis, and used to establish key structure-function relationships. This is a multidisciplinary project incorporating elements of asymmetric chemical catalysis and synthetic biology.

Pic1

Figure 1 The two extremes of catalysis: chemical catalysis (left) and enzymatic catalysis (right) and a hybrid of the two at the interface, based on de novo designed gold coiled coils for asymmetric catalysis.

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.

BBSRC Strategic Research Priority: Industrial Biotechnology and Bioenergy

Techniques that will be undertaken during the project:

The student will gain training and considerable experience in a range of techniques including, peptide design, synthesis and chemical functionalization, solution spectroscopic techniques (such as ultraviolet-visible, fluorescence and circular dichroism spectroscopy), asymmetric catalysis, and structural chemical characterisation.

Contact: Dr Anna Peacock, University of Birmingham