A Surprising (And Surprisingly Useful) Enzymatic Reaction

by David

I never expected an enzyme to do this. When I first learned about the discoveries from Frances Arnold’s lab at Caltech that demonstrated enzymatic cyclopropanation for the first time, I was amazed. I never imagined that an enzyme could catalyze a carbene transfer reaction, in water, with a diazo compound as the carbene source, to produce a chiral cyclopropane product.

Enzyme-catalyzed cyclopropanation was a surprising discovery, a true breakthrough reaction for an enzyme. I also assumed it would probably turn out to be an academic curiosity would be unlikely to find practical use.

But I continued to follow the development of this novel enzymatic cyclopropanation. During the ensuing months the reported turn-over numbers increased. Other carbene and nitrene transfer reactions were demonstrated. As the enzymes were improved through strategic mutations, yields increased dramatically and the production of single stereoisomers was demonstrated with high selectivity. I was impressed.

So impressed, in fact, that I joined the company.

During the last few months our R & D team at Provivi has been focusing on the development of biocatalytic cyclopropanation reactions for practical chemical synthesis. The diversity of the enzyme library and the breadth of scope for stereoselective cyclopropanation reactions have been, and are continually being, being continually expanded.

The potential now exists for this surprising and novel enzymatic reaction to find practical applications, efficiently producing chiral cyclopropane compounds at commercial scale. If you have a chiral cyclopropane target, I think there is reasonable chance that one of these enzymes, perhaps after optimization by directed evolution, can help you produce it more efficiently.

And Provivi wants to make it as easy as possible for customers with cyclopropanation targets to identify an enzyme to produce those compounds.

So, the new Provivi Carbene/Nitrene Transferase enzyme kit is now available.

Screening these breakthrough enzymes is really quite easy … Just add water (and substrates).

These enzymes don’t even need added cofactor.

The reaction is typically fast, yielding product within 1-2 hours, meaning that you can usually have results the same day.

The Provivi Carbene/Nitrene Transferase Kits are now available from Strem Chemicals. (http://www.strem.com/uploads/resources/documents/provivi_carbene-nitrene_transferase_screening_kit_copy1.pdf).

You can also contact me at Provivi with any questions (drozzell@provivi.com), and I promise to respond quickly.

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