Research Project
2106004
ThermoGen proposes to develop a collection of thermostable esterases and lipases which can be used in chiral synthesis of new and safer anticancer and antiviral pharmaceuticals. Phase I feasibility will be demonstrated with discovery of several new enzymes from a variety of extreme- and hyperthermopholic organisms. These enzymes will be grouped by substrates specificities and kinetic properties. A subset of enzymes will be characterized further by gene cloning, protein purification, analysis of thermostability, determination of optimum pH and ionic conditions, and preliminary determination of substrate specificities. Their commercial importance will be assessed, and samples will be tested by industrial pharmaceutical research groups. Phase II will involve expansion of the collection for more specificities and improved properties. Useful enzymes will be more completely characterized by nucleotide sequencing. Organic solvent profiles, and kinetic characterization including product inhibition. Key enzymes will be immobilized and adapted into enzyme screening systems and prototype bioreactors to test for stability and reusability. Finally, to further extend applications, genetic selections will be attempted to modify their substrate specificities and kinetic properties. Phase III will involve the commercialization of the enzymatic activities and adaption and production of the enzymes for large scale chiral chemical synthesis processes.
