Creating Bionic Enzymes

The Science

Newswise — Natural enzymes accomplish the necessary chemical reactions to sustain life. However, these enzymes contain a limited number and type of reactive metal sites, which limits the potential of these enzymes to be used by industry. Scientists re-engineered proteins to allow them to contain a greater range of metals. The result? They created artificial enzymes that can catalyze reactions even for processes where nature never created catalysts.

The Impact

By creating synthetic enzymes, the team opened a new frontier for the design of catalysts that merge the strengths of biological catalysts and chemical catalysts. Merging these strengths enables diverse chemistry that cannot be carried out by classic biological or chemical complexes alone. This research could reduce the cost, time, or waste produced in industrial reactions for biofuels, fossil fuels, and more.

Summary

Enzymes that contain metal ions -- that is, metalloenzymes -- possess the reactivity of a transition metal center and the molecular evolution potential of enzymes. Previously, through molecular engineering, scientists expanded the scope of reactions catalyzed by naturally occurring metalloenzymes to include reactions not performed in nature. However, this strategy is limited by the reactivity of the metal centers in the native metalloenzymes. To overcome this limitation, scientists at Lawrence Berkeley National Laboratory and the University of California, Berkeley replaced the native iron of a metalloenzyme with iridium that behaves differently than iron. The result is artificial enzymes for abiological catalysis within the natural binding site of an enzyme that is suitable for evolution in the laboratory. The artificial enzymes provide reactivity for specific molecules with a high degree of selectivity. More specifically, scientists replaced the iron in the iron-porphyrin complex of myoglobin with the precious metal iridium to create enzymes that catalyze reactions not catalyzed by natural iron-enzymes or other metalloenzymes. The team modified these artificial enzymes to catalyze a large variety of reactions, most notably the conversion of carbon-hydrogen bonds into carbon-carbon bonds, which makes these the first enzymes to catalyze this type of reaction. The presented method of preparing artificial heme proteins containing abiological metal porphyrins sets the stage for the generation of artificial enzymes from nearly limitless combinations of porphyrin-protein structures and non-natural metal cofactors. These synthetic enzymes could catalyze a wide range of abiological transformations. Additionally, as a part of follow-up research, this team has managed to improve the bionic enzymes to match rates found in natural enzymes.

Funding

This work was supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences, and Biosciences under contract DE-AC02- 05CH11231, by the National Science Foundation (graduate research fellowship to H.M.K.), and the Netherlands Organization for Scientific Research (NWO) (Rubicon postdoctoral fellowship 680-50-1306 to P.D.).

Publications

H.M. Key, P. Dydio, D.S. Clark, and J.F. Hartwig, “Abiological catalysis by artificial haem proteins containing noble metals in place of iron.” Nature 534, 534-537 (2016). [DOI: 10.1038/nature17968]

P. Dydio, H.M. Key, A. Nazarenko, J.Y.E. Rha, V. Seyedkazemi, D.S. Clark, and J.F. Hartwig, "An artificial metalloenzyme with the kinetics of native enzymes." Science 354, 102-106 (2016). [DOI: 10.1126/science.aah4427]