Interfacing Microbial Styrene Production with a Biocompatible Cyclopropanation Reaction

Abstract

Introducing new reactivity into living organisms is a major challenge in synthetic biology. Despite an increasing interest in both developing aqueous-compatible small molecule catalysts and engineering enzymes to perform new chemistry in vitro, the integration of non-native reactivity into metabolic pathways for small molecule production has been underexplored. Herein we report a biocompatible iron(III) phthalocyanine catalyst capable of efficient olefin cyclopropanation in the presence of a living microorganism. By interfacing this catalyst with E. coli engineered to produce styrene, we synthesize non-natural phenyl cyclopropanes directly from D-glucose in single-vessel fermentations. This process represents the first combination of non-biological carbene-transfer reactivity with cellular metabolism for small molecule production.