Volume 90 Issue 49 | p. 9 | News of The Week
Issue Date: December 3, 2012

Organometallic Catalyst Works With Natural Enzymes In Reaction Cascades

Artificial metalloenzyme made of iridium complex embedded in protein scaffold cooperates with natural enzymes
Department: Science & Technology
News Channels: Materials SCENE, Biological SCENE
Keywords: catalysis, organometallic, biotechnology, synthesis, reaction cascade
[+]Enlarge
WORKING TOGETHER
In this reaction cascade, an enzyme turns substrates into intermediates that are then used by an artificial metalloenzyme to form products.
Credit: Adapted from Nat. Chem.
Schematic showing natural enzyme working in concert with an artificial metalloenzyme in a cascade reaction. Structure is of the organometallic catalyst that is embedded in streptavidin to make artificial metalloenzyme.
 
WORKING TOGETHER
In this reaction cascade, an enzyme turns substrates into intermediates that are then used by an artificial metalloenzyme to form products.
Credit: Adapted from Nat. Chem.

Transition-metal catalysts and biological catalysts don’t always play nicely. In fact, like playground bullies, they can be downright mean, shutting each other down. But now, an international team of chemists has found a way to make them friends. Making organometallic catalysts and enzymes compatible with one another could expand the range of reactions available for industrial biotechnology, such as the production of new types of biofuels.

The team—Thomas R. Ward of the University of Basel, in Switzerland; Nicholas J. Turner of the University of Manchester, in England; and Frank Hollmann of Delft University of Technology, in the Netherlands; and coworkers—has developed an artificial metalloenzyme that works in reaction cascades with multiple natural enzymes (Nat. Chem., DOI: 10.1038/nchem.1498).

This combination has been tough to achieve. “For many years, biocatalysts and organometallic catalysts have been developed separately,” says Yi Lu, a chemistry professor at the University of Illinois, Urbana-Champaign. “Although much effort has been devoted to combining the two fields, the incompatibility between the two types of catalysts has made it difficult to realize the promise, particularly in carrying out cascade reactions like those observed in biology.” The new work shows that an artificial metalloenzyme containing an organometallic center is “not only compatible with native enzymes but can also work in harmony with them to perform several cascade reactions,” Lu says.

The researchers made an artificial transfer hydrogenase by embedding an iridium catalyst in a streptavidin scaffold. The streptavidin pocket protects the catalyst and prevents it from inactivating enzymes. “We’re keeping systems that are ‘allergic’ to each other apart,” Ward says.

The researchers used genetic engineering to improve the metalloenzyme. “The organometallic catalyst alone is already active in the absence of any enzyme that inhibits it,” Ward says. “When inserted in streptavidin, the artificial metalloenzyme becomes compatible with a variety of natural enzymes. Thanks to genetic engineering coupled with a colorimetric assay, we also significantly improved the performance of the artificial metalloenzyme.”

The researchers used the artificial transfer hydrogenase in reaction cascades with several other enzymes. For instance, they coupled it with a monoamine oxidase to catalyze the double stereoselective deracemization of amines. In addition, they made a four-enzyme cascade to synthesize l-pipecolic acid from l-lysine.

“The authors have shown how molecular compartmentalization of organometallic catalysts can increase the efficiency of biocatalytic cascades and enable new cascades,” says Claudia Schmidt-Dannert, a biologist at the University of Minnesota, Twin Cities. “This work is just at the beginning of how protein scaffolds can be engineered and fitted with completely unnatural cofactors designed in the chemistry lab to perform novel types of enzyme reactions.”

 
Chemical & Engineering News
ISSN 0009-2347
Copyright © American Chemical Society

Leave A Comment

*Required to comment