Abstract
The ability of hydrogenase enzymes to activate H(2) with excellent selectivity leads to many interesting possibilities for biotechnology driven by H(2) as a clean reductant. Here, we review examples where hydrogenase enzymes have been used to drive native and non-native hydrogenation reactions in solution or as part of a redox cascade on a conductive support, with a focus on the developments we have contributed to this field. In all of the examples discussed, hydrogenation reactions are enabled by coupled redox reactions: the oxidation of H(2) at a hydrogenase active site, linked electronically (via relay clusters in the enzyme and/or via conductive support) to the site of a reduction reaction, and we note how this parallels developments in site-separated reactivity in heterogeneous catalysis. We discuss the productivities achieved with biocatalytic hydrogenations, the scope for application of these approaches in industrial biotechnology, possibilities for scaling the production of hydrogenases, and future opportunities. Our focus is on NiFe hydrogenases, but we discuss briefly how FeFe hydrogenases might contribute to this field.