Work

Enzymatic construction of highly strained carbocycles

Year: 2018

Type: article

Abstract: Double rings made with heme Cyclic organic structures with adjacent three-carbon rings—bicyclobutanes—are useful starting materials for chemical and materials synthesis owing to their extreme ring strain. Constructing these molecules is a challenging task for organic chemists, especially if a single stereoisomer is desired. Chen et al. engineered a heme-containing enzyme to catalyze sequential carbene insertion reactions using an alkyne substrate. Starting with an enzyme that could only catalyze a single carbene insertion, a series of mutations led to variants that catalyzed efficient, stereoselective production of bicyclobutanes. By using a less reactive alkyne substrate and screening more variants with active site mutations, the authors found enzymes that stop at either enantiomer of the intermediate cyclopropene. Science , this issue p. 71

Source: Science

DOI: 10.1126/science.aar4239

Authors: Kai Chen, Xiongyi Huang, S. B. Jennifer Kan, Ruijie K. Zhang, Frances H. Arnold

Institution: California Institute of Technology

Language: English

Topic: Cyclopropane Reaction Mechanisms

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: green

Funders: National Science Foundation, National Institutes of Health, Donna and Benjamin M. Rosen Bioengineering Center, California Institute of Technology, National Institute of General Medical Sciences

Awards: Expanding the Enzyme Repertoire by Evolution and Engineering, Graduate Research Fellowship Program (GRFP), A Biocatalytic System for Enantioselective Carbon-Boron Bond Formation