Engineering a dirhodium artificial metalloenzyme for selective olefin cyclopropanation

Area of Science:

• Biocatalysis and synthetic chemistry
• Protein engineering and catalyst design

Background:

• Artificial metalloenzymes (ArMs) integrate synthetic catalysts into protein scaffolds.
• ArMs offer enhanced selectivity compared to traditional metal catalysts.
• Dirhodium complexes are versatile catalysts but can suffer from low selectivity and water sensitivity.

Purpose of the Study:

• To create a novel artificial metalloenzyme for olefin cyclopropanation.
• To improve the enantioselectivity and substrate scope of the cyclopropanation reaction.
• To enhance the water tolerance of dirhodium-catalyzed reactions.

Main Methods:

• Covalent linkage of an alkyne-substituted dirhodium catalyst to a modified prolyl oligopeptidase.
• Genetic encoding of L-4-azidophenylalanine for catalyst attachment.
• Scaffold mutagenesis to optimize catalyst performance.
• Testing cyclopropanation with various styrenes and carbene precursors.

Main Results:

• Successful creation of an ArM catalyzing olefin cyclopropanation.
• Improved enantioselectivity achieved through scaffold mutagenesis.
• Broad substrate scope demonstrated with diverse styrenes and carbene precursors.
• Significant reduction in byproduct formation, including water-mediated side reactions.

Conclusions:

• The developed ArM enhances substrate specificity and water tolerance of metal catalysis.
• This work demonstrates the potential of ArMs to overcome limitations of traditional metal catalysts.
• Dirhodium ArMs present new avenues for highly selective catalytic transformations.