Swapping out myoglobin’s iron and installing iridium in its place has resulted in an artificial metalloenzyme. In this image, the protein (grey) wraps around a disk-like porphyrin (red), a component of natural heme proteins. At the center of the heme sits iridium (purple), which acts as the metalloenzyme’s active site. The metalloenzyme converts the molecules at the top to those at the bottom by reaction at a carbon-hydrogen bond (left) and carbon-carbon double bond (right), respectively. [John Hartwig Group/Berkeley Lab and UC Berkeley]
Swapping out myoglobin’s iron and installing iridium in its place has resulted in an artificial metalloenzyme. In this image, the protein (grey) wraps around a disk-like porphyrin (red), a component of natural heme proteins. At the center of the heme sits iridium (purple), which acts as the metalloenzyme’s active site. The metalloenzyme converts the molecules at the top to those at the bottom by reaction at a carbon-hydrogen bond (left) and carbon-carbon double bond (right), respectively. [John Hartwig Group/Berkeley Lab and UC Berkeley]

We can rebuild it. We have the technology. We can make it better than it was. Better…stronger…faster.

With apologies to Oscar Goldman, the “it” here isn’t an expensive cyborg, but rather an iridium-substituted myoglobin, a metalloprotein that is ordinarily built around iron. With a noble metal at its heart rather than the common transition metal, myoglobin expands its chemical powers. Specifically, it becomes capable of converting a carbon–hydrogen bond to a carbon–carbon single bond. In fact, the iridium-substituted myoglobin catalyzes a reaction for which there is no known natural or engineered enzyme.

Because the iridium-substituted myoglobin is still natural, but not quite natural, it is, in a sense, “bionic.” It could also be called, less extravagantly, “abiotic,” as it was in an article that appeared June 13 in the journal Nature. The article, entitled “Abiological Catalysis by Artificial Haem Proteins Containing Noble Metals in Place of Iron,” described how DOE/Lawrence Berkeley National Laboratory scientists tried to get the best of both worlds—chemical catalysts and biological catalysts. Chemical catalysts built from precious metals enable a much larger set of reactions than enzymes. But enzymes are highly specific. Most important, they catalyze the chemical reactions in living organisms.

“Many enzymes contain metals, but that metal is usually iron or copper, and the set of reactions catalyzed by iron or copper is much smaller than the set of reactions catalyzed by the precious metals,” said John Hartwig, Ph.D., a senior faculty scientist in Berkeley Lab's Chemical Sciences Division. “Enzymes catalyze reactions necessary for life, not the reactions needed to create the everyday objects around us. We found a way to replace the iron in the protein myoglobin with a precious metal, which resulted in an artificial enzyme that has the diverse reactivity of the precious metal combined with the high selectivity and capability to function under mild conditions found in an enzyme.”

In the Nature article, Dr. Hartwig and colleagues described how they replaced the iron in Fe-porphyrin IX (Fe-PIX) proteins with abiological, noble metals to create enzymes that catalyze reactions not catalyzed by native Fe-enzymes or other metalloenzymes.

“We prepared modified myoglobins containing an Ir(Me) site that catalyse the functionalization of C–H bonds to form C–C bonds by carbene insertion and add carbenes to both β-substituted vinylarenes and unactivated aliphatic α-olefins,” wrote the articles’ authors. “We conducted directed evolution of the Ir(Me)-myoglobin and generated mutants that form either enantiomer of the products of C–H insertion and catalyse the enantio- and diastereoselective cyclopropanation of unactivated olefins.”

The researchers started by manipulating Escherichia coli bacteria to create myoglobin that lacked iron. They then incorporated iridium into the muscle protein at the site where iron would normally be. Experiments showed that iridium could be bound at the site typically occupied by iron so that myoglobin could function as a new enzyme.

“Perhaps most important, this new artificial enzyme can be evolved in the laboratory to selectively form one product over another,” noted Dr. Hartwig. “We want to take the catalysts that chemists have created and combine them with naturally occurring enzymes. We can use that structure to control the selectivity of the products created.”

Essentially, Dr. Hartwig’s team found a novel way to combine two different types of catalysts. Preparing artificial heme proteins containing abiological metal porphyrins could lead to the generation of artificial enzymes to catalyze a wide range of abiological transformations.

“This is the first proof of principle of a new strategy to catalysis,” stated Dr. Hartwig. “We've synthetically changed a protein to give it the functionality of a chemical catalyst while keeping in enough of the biology to allow us to use methods of molecular biology to evolve new functions. The long-term potential of this approach seems limitless.”








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