Professor Pedro J. de Pablo has been awarded collaborative Research Grant from the Human Frontier Science Program entitled “Protein nanocages as single molecular reactors to understand biocatalysis in crowded environments”.
Almost everything we know about biocatalysis comes from in vitro studies, which are difficult to connect to biophysical parameters important for in vivo enzyme behavior. These large biomolecular ensembles provide average results that may suppress significant individualized details. We aim to understand how multiple enzymes in a pathway behave in concert with control over biophysical parameters that mimic cellular conditions. This objective requires designing systems able to control the environment of enzymes while measuring their catalysis in real time. Here we propose to pack tens of enzymes within protein cages. This approach allows exquisite control over the environment in which proteins operate and the physical manipulation and measurement of their behavior can be achieved with ensemble and single-molecule techniques. This approach will allow us to examine and simulate at the nanoscale how enzymes behave in response to changes in molecular crowding, substrate flux, and metabolite-level regulation in an in vivo mimicking system. We will apply these tools to understand flux control of the MEP isoprenoid pathway, responsible for production of essential secondary metabolites that fulfill myriad roles in biology and have significant industrial applications.
Besides Prof. de Pablo, in this collaborative project will participate Prof. Claudia Vickers (Australian Institute for Bioengineering and Nanotechnology, The University of Queensland) and Prof. Trevor Douglas (Chemistry Department, Indiana University).
The award is of 350,000 USD per year for a period of three years, and the success rate is about 4%. [Press release HFSP Awards 2018]
We congratulate Pedro J. de Pablo.