Enzymatic construction of highly strained carbocycles

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