Integrated Calendar

The application of enzymes to solve important problems has evolved over hundreds of years but has still not yet reached its fullest potential. The activity of enzymes in their natural state, in their ideal environment, and with their natural substrates is often much greater than needed ex vivo, thus driving intense research in activity enhancement. The inability to reach highly effective catalytic rates in harsh environments and against unnatural substrates has led to a number of elegant methods to modify enzyme structure and function. Lessons learned from molecular genetics, adaptation to organic solvents, immobilization, and conjugation with small molecules and polymers have greatly increased the activity of enzymes outside of their natural environments. For some applications, current protein engineering technologies have resulted in highly productive reagents. For many other applications, optimized solutions have been elusive. An evolution of our understanding of enzyme immobilization and polymer-protein conjugation has led to the emergence of polymer-based protein engineering (PBPE). We have developed and applied techniques that allow us to design and synthesize polymers directly from the protein surface. The process allows us to saturate conjugation sites, and by growing the polymers using atom transfer radical polymerization (ATRP), to control polymer size and structure. PBPE thus offers an attractive method to predictably modify and enhance enzyme structure and function. Using polymers that respond to stimuli such as temperature and pH, enzyme activity and stability can be predictably modified without a dependence on molecular biology. We have demonstrated that temperature responsive enzyme-polymer conjugates show increased stability while retaining bioactivity and substrate affinity. We are currently working on specific modifications of a number of proteins for a wide variety of uses such as oral therapeutics, biofuel cells, molecular sieves, proteomic applications, and agent decontamination.