Biological catalysis, synthetic biology and biomolecular engineering.
I have been fascinated by the complexity and catalytic capabilities of enzymes throughout my career. My group has pursued research on the mechanisms and structures of biocatalysts - and more recently on light-responsive proteins - and integrated these studies into ambitious synthetic biology and metabolic engineering programmes (e.g. for chemicals production). At the basic discovery science end of the spectrum, my group has undertaken ambitious, wide-ranging interdisciplinary programmes in experimental enzyme biophysics and integrated these with structural and chemical biology, computational simulation and theory. Publications from the group reflect contributions from across these key discipline areas. Highlights have included demonstration of the unexpected importance of nuclear tunneling mechanisms in biological catalysis, discovery of new biological cofactors (e.g. prenylated flavins), structures of enzymes in complex with lead drug compounds (e.g. for Huntington's chorea/Alzheimer's disease) and mechanistic understanding of new roles for vitamin B12 and other photoreceptors in light-activated transcriptional regulation. In the fields of metabolic engineering/synthetic biology/directed evolution we have engineered organisms to biosynthesize propane gas and a wide array of monoterpenoid products. These programmes have their foundations in basic discovery science and in selected cases extend to commercial exploitation through spin out activity. We have established novel biophysics and synthetic biology infrastructure at Manchester to support this work including two major research centres in MIB: SYNBIOCHEM (Synthetic Biology Research Centre for Fine and Speciality Chemicals) and a biophysics facility (the Manchester Centre for Biophysics and Catalysis), which includes ultrafast laser UV, fluorescence up-conversion and IR spectroscopy as well as a suite of advanced time-resolved spectoscopies for analysis of enzyme mechanisms. We have also established a new national Centre of Excellence in biomanufacturing (UK Future Biomanufacturing Research Hub) to work closely with industry to biomanufacture pharmaceuticals, high value chemicals and engineering materials. Given the breadth of the work in the group, we have a large research team (ca 50 staff) and strong collaborations with specialists in other disciplines (e.g. synthetic chemistry; materials science), both within MIB and external to Manchester.
Keywords: enzyme biocatalysts • quantum biology • quantum tunnelling • photochemistry • enzyme design • directed evolution • enzyme mechanisms • enzyme structures and dynamics • synthetic biology • chemicals biosynthesis • nanoscale bioengineering • biocatalysis • metabolic engineering