Interfacing microbial styrene production with a biocompatible cyclopropanation reaction.
The introduction of new reactivity into living organisms is a major challenge in synthetic biology. Despite an increasing interest in both the development of small-molecule catalysts that are compatible with aqueous media and the engineering of 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 synthesized non-natural phenyl cyclopropanes directly from D-glucose in single-vessel fermentations. This process is the first example of the combination of nonbiological carbene-transfer reactivity with cellular metabolism for small-molecule production.
Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138 (USA) http://scholar.harvard.edu/balskus.
Stephen
S
Wallace
Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138 (USA) http://scholar.harvard.edu/balskus. balskus@chemistry.harvard.edu.
Emily P
EP
Balskus
D002384:Catalysis; D003521:Cyclopropanes / Q000737:chemistry* / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D005290:Ferric Compounds / Q000737:chemistry; D005947:Glucose / Q000378:metabolism; D007211:Indoles / Q000737:chemistry; D054833:Isoindoles; D008697:Methane / Q000031:analogs & derivatives / Q000737:chemistry; D020058:Styrene / Q000737:chemistry / Q000378:metabolism
D003521:Cyclopropanes; D005290:Ferric Compounds; D007211:Indoles; D054833:Isoindoles; C030011:carbene; D020058:Styrene; D005947:Glucose; D008697:Methane; C013647:phthalocyanine
iron; metabolism; phthalocyanine; synthetic biology; synthetic methods