title: Sugar Synthesis from CO2 in Escherichia coli.
abstract: Can a heterotrophic organism be evolved to synthesize biomass from CO2 directly? So far, non-native carbon fixation in which biomass precursors are synthesized solely from CO2 has remained an elusive grand challenge. Here, we demonstrate how a combination of rational metabolic rewiring, recombinant expression, and laboratory evolution has led to the biosynthesis of sugars and other major biomass constituents by a fully functional Calvin-Benson-Bassham (CBB) cycle in E. coli. In the evolved bacteria, carbon fixation is performed via a non-native CBB cycle, while reducing power and energy are obtained by oxidizing a supplied organic compound (e.g., pyruvate). Genome sequencing reveals that mutations in flux branchpoints, connecting the non-native CBB cycle to biosynthetic pathways, are essential for this phenotype. The successful evolution of a non-native carbon fixation pathway, though not yet resulting in net carbon gain, strikingly demonstrates the capacity for rapid trophic-mode evolution of metabolism applicable to biotechnology. PAPERCLIP.
authors.affiliation: Department of Plant and Environmental Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Niv
authors.initials: N
authors.lastname: Antonovsky
authors.affiliation: Department of Plant and Environmental Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Shmuel
authors.initials: S
authors.lastname: Gleizer
authors.affiliation: Department of Plant and Environmental Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Elad
authors.initials: E
authors.lastname: Noor
authors.affiliation: Department of Plant and Environmental Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Yehudit
authors.initials: Y
authors.lastname: Zohar
authors.affiliation: Department of Plant and Environmental Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Elad
authors.initials: E
authors.lastname: Herz
authors.affiliation: Department of Plant and Environmental Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Uri
authors.initials: U
authors.lastname: Barenholz
authors.affiliation: Department of Plant and Environmental Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Lior
authors.initials: L
authors.lastname: Zelcbuch
authors.affiliation: Department of Plant and Environmental Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Shira
authors.initials: S
authors.lastname: Amram
authors.affiliation: Department of Plant and Environmental Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Aryeh
authors.initials: A
authors.lastname: Wides
authors.affiliation: Department of Computer Science, Technion, Israel Institute of Technology, Haifa 3200003, Israel.
authors.forename: Naama
authors.initials: N
authors.lastname: Tepper
authors.affiliation: Department of Plant and Environmental Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Dan
authors.initials: D
authors.lastname: Davidi
authors.affiliation: Department of Plant and Environmental Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Yinon
authors.initials: Y
authors.lastname: Bar-On
authors.affiliation: Department of Plant and Environmental Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Tasneem
authors.initials: T
authors.lastname: Bareia
authors.affiliation: Department of Plant and Environmental Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: David G
authors.initials: DG
authors.lastname: Wernick
authors.affiliation: Department of Plant and Environmental Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Ido
authors.initials: I
authors.lastname: Shani
authors.affiliation: Department of Plant and Environmental Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Sergey
authors.initials: S
authors.lastname: Malitsky
authors.affiliation: Department of Biological Services, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Ghil
authors.initials: G
authors.lastname: Jona
authors.affiliation: Department of Plant and Environmental Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Arren
authors.initials: A
authors.lastname: Bar-Even
authors.affiliation: Department of Plant and Environmental Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel. Electronic address: ron.milo@weizmann.ac.il.
authors.forename: Ron
authors.initials: R
authors.lastname: Milo
mesh_terms: D052818:Autotrophic Processes; D002241:Carbohydrates / Q000096:biosynthesis; D002245:Carbon Dioxide / Q000378:metabolism*; D019020:Directed Molecular Evolution; D004926:Escherichia coli / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D005943:Gluconeogenesis; D013058:Mass Spectrometry; D053858:Metabolic Networks and Pathways
chemical_list: D002241:Carbohydrates; D002245:Carbon Dioxide