Predicting Enzyme Reactivity

About

Applications This technology provides methods for rapidly finding selective and highly active P450-based oxidation catalysts for the oxyfunctionalization (i.e. hydroxylation, epoxidation) of a target organic molecule. This method is particularly useful for developing synthetic procedures that enable the functional elaboration of a high-value compound (e.g. natural product, lead compound, drug molecule) at poorly reactive or unreactive C?H sites. Accordingly, these methods can be useful in drug discovery and development campaigns toward obtaining analogs of a molecule of interest that possess improved physico-chemical, pharmacokinetic, and/or pharmacological properties. In addition, the use of these enzyme-based catalysts enable more concise, inexpensive and environmentally-friendly synthetic procedures to produce these high-value compounds. This invention also describes methods for a) generating high-quality libraries of engineered monooxygenases, and b) enabling the identification of monooxygenases with a pre-defined function.   Advantages Currently, chemical catalysts that are used for selective oxidation of aliphatic C-H bonds in transformations for producing high value compounds have several drawbacks. These include the need for harsh reaction conditions and toxic metals, low selectivity, and low catalytic activity. Cytochrome P450s, however, are naturally occurring enzymes that can perform this transformation under mild conditions, but the current methods for the discovering or engineering suitable P450s for the desired transformation is a laborious, time consuming process. This technology provides a method that can accelerate the P450 catalyst optimization by orders of magnitudes compared to current approaches.