title: A synthetic pathway for the fixation of carbon dioxide in vitro.
abstract: Carbon dioxide (CO2) is an important carbon feedstock for a future green economy. This requires the development of efficient strategies for its conversion into multicarbon compounds. We describe a synthetic cycle for the continuous fixation of CO2in vitro. The crotonyl-coenzyme A (CoA)/ethylmalonyl-CoA/hydroxybutyryl-CoA (CETCH) cycle is a reaction network of 17 enzymes that converts CO2into organic molecules at a rate of 5 nanomoles of CO2per minute per milligram of protein. The CETCH cycle was drafted by metabolic retrosynthesis, established with enzymes originating from nine different organisms of all three domains of life, and optimized in several rounds by enzyme engineering and metabolic proofreading. The CETCH cycle adds a seventh, synthetic alternative to the six naturally evolved CO2fixation pathways, thereby opening the way for in vitro and in vivo applications.
authors.affiliation: Biochemistry and Synthetic Biology of Microbial Metabolism Group, Max Planck Institute for Terrestrial Microbiology Marburg, D-35043 Marburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schwander
authors.affiliation: Biochemistry and Synthetic Biology of Microbial Metabolism Group, Max Planck Institute for Terrestrial Microbiology Marburg, D-35043 Marburg, Germany.|Institute for Microbiology, ETH Zürich, CH-8093 Zürich, Switzerland.
authors.forename: Lennart
authors.initials: L
authors.lastname: Schada von Borzyskowski
authors.affiliation: Biochemistry and Synthetic Biology of Microbial Metabolism Group, Max Planck Institute for Terrestrial Microbiology Marburg, D-35043 Marburg, Germany.|Institute for Microbiology, ETH Zürich, CH-8093 Zürich, Switzerland.
authors.forename: Simon
authors.initials: S
authors.lastname: Burgener
authors.affiliation: Biochemistry and Synthetic Biology of Microbial Metabolism Group, Max Planck Institute for Terrestrial Microbiology Marburg, D-35043 Marburg, Germany.
authors.forename: Niña Socorro
authors.initials: NS
authors.lastname: Cortina
authors.affiliation: Biochemistry and Synthetic Biology of Microbial Metabolism Group, Max Planck Institute for Terrestrial Microbiology Marburg, D-35043 Marburg, Germany. toerb@mpi-marburg.mpg.de.|Institute for Microbiology, ETH Zürich, CH-8093 Zürich, Switzerland.|LOEWE Center for Synthetic Microbiology, Universität Marburg, D-35037 Marburg, Germany.
authors.forename: Tobias J
authors.initials: TJ
authors.lastname: Erb
mesh_terms: D000214:Acyl Coenzyme A / Q000737:chemistry / Q000235:genetics; D017360:Arabidopsis / Q000201:enzymology; D053898:Biosynthetic Pathways; D002244:Carbon / Q000737:chemistry; D057486:Carbon Cycle; D002245:Carbon Dioxide / Q000737:chemistry*; D010088:Oxidoreductases / Q000737:chemistry / Q000235:genetics; D015202:Protein Engineering; D012242:Rhodobacter sphaeroides / Q000201:enzymology; D058615:Synthetic Biology
chemical_list: D000214:Acyl Coenzyme A; C102829:ethylmalonyl-coenzyme A; D002245:Carbon Dioxide; D002244:Carbon; C010701:crotonyl-coenzyme A; D010088:Oxidoreductases