A Blueprint for Catalytic Promiscuity in de novo Designed Enzymes

1:00pm - 2:00pm / Monday 11th November 2019 / Venue: LT1 Life Sciences Building
Type: Seminar / Category: Research / Series: GSTT Seminar Series
  • Suitable for: Those with an interest in Genomes, Systems and Therapeutic Targeting
  • Admission: Free
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Speaker: Ross Anderson (University of Bristol)

Bespoke protein catalysts compatible with the natural biomolecular components of living cells are key to realizing the ambitious goals of synthetic biology and to the provision of cheap, green catalysts for industrial biotechnology. To this end, I believe that simple, de novo proteins naïve to the evolutionary process can provide excellent scaffolds for enzyme design, and here I highlight the work of my lab in constructing heme-containing de novo proteins that exhibit both biologically relevant and abiotic catalytic activities that equal and surpass those of many natural and engineered enzymes. I will show how a relatively simple design process is sufficient to create C45, a thermostable, artificial c-type cytochrome with exceptionally diverse catalytic activities – including peroxidase, oxidative dehalogenase and carbene transferase activities – that is fully assembled and catalytically active in vivo. Since C45 exhibits a high tolerance to organic solvents, I will also highlight my group’s work in encapsulating C45 into hydrogel beads, producing a versatile heterogeneous catalyst formulation that maintains the enzymatic activity of the de novo enzyme even in neat non-polar organic solvents. Finally, I will describe our recent design of b-type heme-containing proteins, demonstrating how fundamental biophysical properties such as redox potential can be successfully and precisely selected in silico.