Hemoprotein Catalyzed Oxygenations: P450s, UPOs, and Progress toward Scalable Reactions.

The selective oxygenation of non-activated carbon atoms is an ongoing synthetic challenge and biocatalysts, particularly hemoprotein oxygenases, continue to be investigated for their potential, given both their sustainable chemistry credentials and also their superior selectivity. However, issues of stability, activity and complex reaction requirements often render these biocatalytic oxygenations problematic with respect to scalable industrial processes. A continuing focus on Cyto-chromes P450 (P450s), which require a reduced nicotinamide cofactor and redox protein partners for electron transport, has now led to better catalysts and processes with a greater understanding of process requirements and limitations for both in vitro and whole-cell systems. However, the discovery and development of unspecific peroxygenases (UPOs) has also recently provided valuable complementary technology to P450-catalyzed reactions. UPOs need only hydrogen peroxide to effect ox-ygenations but are hampered by their sensitivity to peroxide and also by limited selectivity. In this perspective we survey recent developments in the engineering of proteins, cells and processes for oxygenations by these two groups of hemopro-teins and evaluate their potential and relative merits for scalable reactions.