Engineering Cytochrome P450s for Enantioselective Cyclopropenation of Internal Alkynes

Research Overview

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Graduate student and Resnick Fellow, Kai Chen, and his faculty advisor Frances Arnold recently developed a versatile biocatalytic platform of engineered cytochrome P450 enzymes to carry out efficient cyclopropene synthesis via carbene transfer to internal alkynes. The results of this study are summarized in the publication, "Engineering Cytochrome P450s for Enantioselective Cyclopropenation of Internal Alkynes", which notes the engineered P450 enzymes accommodated diverse internal alkynes for cyclopropenation with unprecedented efficiencies and selectivities.

Scientific Achievement

We evolved cytochrome P450 enzymes to carry out efficient cyclopropene synthesis via carbene transfer to internal alkynes.

Significance and Impact

The engineered P450 enzymes, as genetically encoded biocatalysts, accommodated diverse internal alkynes for cyclopropenation with unprecedented efficiencies and selectivities.

Directed evolution of a P450 variant, P411-C10, led to a lineage of engineered P450 enzymes, capable of catalyzing highly efficient and selective synthesis of synthetically useful, highly strained cyclopropenes from internal alkynes. Directed evolution of a P450 variant, P411-C10, led to a lineage of engineered P450 enzymes, capable of catalyzing highly efficient and selective synthesis of synthetically useful, highly strained cyclopropenes from internal alkynes. Credit: Reprinted with permission from Kai Chen and Frances H. Arnold Journal of the American Chemical Society 2020 142 (15), 6891-6895 DOI: 10.1021/jacs.0c01313 (2020) American Chemical Society.

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Directed evolution of a P450 variant, P411-C10, led to a lineage of engineered P450 enzymes, capable of catalyzing highly efficient and selective synthesis of synthetically useful, highly strained cyclopropenes from internal alkynes. Directed evolution of a P450 variant, P411-C10, led to a lineage of engineered P450 enzymes, capable of catalyzing highly efficient and selective synthesis of synthetically useful, highly strained cyclopropenes from internal alkynes.

Credit: Reprinted with permission from Kai Chen and Frances H. Arnold Journal of the American Chemical Society 2020 142 (15), 6891-6895 DOI: 10.1021/jacs.0c01313 (2020) American Chemical Society.

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Technical Details

• Directed evolution of cytochrome P450 enzymes.
• Highly enantioselective synthesis of internal cyclopropenes (as pure enantiomers).

Kai Chen and Frances H. Arnold. Engineering Cytochrome P450s for Enantioselective Cyclopropenation of Internal Alkynes (2020) J. Am. Chem. Soc. DOI: 10.1021/jacs.0c01313

Contact: Frances H. Arnold