A Regioselective Biocatalyst for Alkane Activation under Mild Conditions

摘要

The activation of alkanes to provide compounds of high value is an important scientific challenge. Increasing environmental concerns call for the design of alternative and efficient oxidation routes under mild conditions. Such benign methods should enable the problems associated with the use of toxic acids, solvents, and metals to be circumvented, and should enable reactions to be carried out in an aqueous medium at low temperature with a clean oxidant, such as oxygen. The use of biological catalysts instead of chemical catalysts can be advantageous, because difficult reactions can often be performed under mild conditions. Indeed, alkanes are particularly inert molecules, and their selective transformation remains an important problem.Cytochromes P450 (CYP) form a superfamily of enzymes widely distributed from prokaryotes to superior eukaryotes. They are known to catalyze the monooxygenation of a large variety of hydrophobic chemical compounds, such as alkanes, xenobiotics, steroids, and prostaglandins. An important element for P450 catalysis is the nicotinamide adenine dinucleotide cofactor, which, in its reduced form (NADH or NADPH), provides the electrons necessary for the catalytic cycle. As the electrons cannot be transferred directly to the heme prosthetic group, redox protein partner(s) (P450 reductase) should be present to shuttle the reducing equivalents from NAD(P)H to the hydroxylase domain (Scheme 1). Slow or uncoupled electron transfer currently limits the catalytic efficiency of P450s.