This project aims to use modern synthetic biology and synthetic chemistry techniques to create new recombinant microbes for use in synthetic biotechnology. In particular, we are interested in engineering E. coli cells to perform reaction sequences that are not found in Nature.
The first aim of this project will be to use unnatural amino acid incorporation (via AMBER stop codon suppression) and bioconjugation chemistry to anchor non-enzymatic catalysts to the surface and interior structures of the E. coli cell membrane. This will allow the systematic examination of non-enzymatic catalysis in these cellular environments – an underexplored area of biocompatible chemistry. These findings will then be compared to other methods of membrane localisation. These include the use of membrane-localising chemical tags and engineered exopolysaccharide slimes.
The second aim of this project will be to use this approach in conjunction with de novo biosynthetic pathway design in E. coli. This will enable the in situ modification of metabolites in fermentations and create a new way of producing non-natural molecules directly from renewable starting materials.[2,3]
The multi-disciplinary nature of this project will allow students to develop a strong proficiency in cellular engineering techniques (both chemical and genetic), whole-cell biocatalysis and organic synthesis. This project will likely be best suited to students from a biotechnology/biochemistry/organic synthesis background with an interest in synthetic biology, synthetic organic chemistry and/or the production of small molecules via microbial fermentation.
This project will be co-supervised by Prof. Susan Rosser and Dr Stephen Wallace in the Institute of Quantitative Biology, Biochemistry and Biotechnology (IQB3) at the University of Edinburgh. This research will expose students to a variety of techniques including unnatural amino acid incorporation (Wallace/Rosser), recombinant DNA assembly (Rosser), synthetic biology (Rosser), in vivo bioconjugation (Wallace), and synthetic organic chemistry (Wallace).
 S. Wallace, E. P. Balskus, Curr. Opin. Biotechnol. 2014, 30, 1–8
 S. Wallace, E. P. Balskus, Angew. Chem. Int. Ed. 2016, 55, 6023–6027
 S. Wallace, E. P. Balskus, Angew. Chem. Int. Ed. 2015, 54, 7106–7109