PMID- 33199707
OWN - NLM
STAT- MEDLINE
DCOM- 20201125
LR  - 20201125
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 11
IP  - 1
DP  - 2020 Nov 16
TI  - Awakening a latent carbon fixation cycle in Escherichia coli.
PG  - 5812
LID - 10.1038/s41467-020-19564-5 [doi]
LID - 5812
AB  - Carbon fixation is one of the most important biochemical processes. Most natural 
      carbon fixation pathways are thought to have emerged from enzymes that originally 
      performed other metabolic tasks. Can we recreate the emergence of a carbon 
      fixation pathway in a heterotrophic host by recruiting only endogenous enzymes? 
      In this study, we address this question by systematically analyzing possible 
      carbon fixation pathways composed only of Escherichia coli native enzymes. We 
      identify the GED (Gnd-Entner-Doudoroff) cycle as the simplest pathway that can 
      operate with high thermodynamic driving force. This autocatalytic route is based 
      on reductive carboxylation of ribulose 5-phosphate (Ru5P) by 6-phosphogluconate 
      dehydrogenase (Gnd), followed by reactions of the Entner-Doudoroff pathway, 
      gluconeogenesis, and the pentose phosphate pathway. We demonstrate the in vivo 
      feasibility of this new-to-nature pathway by constructing E. coli gene deletion 
      strains whose growth on pentose sugars depends on the GED shunt, a linear variant 
      of the GED cycle which does not require the regeneration of Ru5P. Several 
      metabolic adaptations, most importantly the increased production of NADPH, assist 
      in establishing sufficiently high flux to sustain this growth. Our study 
      exemplifies a trajectory for the emergence of carbon fixation in a heterotrophic 
      organism and demonstrates a synthetic pathway of biotechnological interest.
FAU - Satanowski, Ari
AU  - Satanowski A
AUID- ORCID: 0000-0003-0775-4799
AD  - Max Planck Institute of Molecular Plant Physiology, Am Muhlenberg 1, 14476, 
      Potsdam, Germany.
FAU - Dronsella, Beau
AU  - Dronsella B
AUID- ORCID: 0000-0002-5541-3289
AD  - Max Planck Institute of Molecular Plant Physiology, Am Muhlenberg 1, 14476, 
      Potsdam, Germany.
FAU - Noor, Elad
AU  - Noor E
AUID- ORCID: 0000-0001-8776-4799
AD  - Institute of Molecular Systems Biology, ETH Zurich, Otto-Stern-Weg 3, 8093, 
      Zurich, Switzerland.
FAU - Vogeli, Bastian
AU  - Vogeli B
AD  - Max Planck Institute for Terrestrial Microbiology, Karl-von-Frisch-Strasse 10, 
      35043, Marburg, Germany.
FAU - He, Hai
AU  - He H
AUID- ORCID: 0000-0003-1223-2813
AD  - Max Planck Institute of Molecular Plant Physiology, Am Muhlenberg 1, 14476, 
      Potsdam, Germany.
FAU - Wichmann, Philipp
AU  - Wichmann P
AD  - Max Planck Institute of Molecular Plant Physiology, Am Muhlenberg 1, 14476, 
      Potsdam, Germany.
FAU - Erb, Tobias J
AU  - Erb TJ
AUID- ORCID: 0000-0003-3685-0894
AD  - Max Planck Institute for Terrestrial Microbiology, Karl-von-Frisch-Strasse 10, 
      35043, Marburg, Germany.
AD  - Center for Synthetic Microbiology (SYNMIKRO), 35043, Marburg, Germany.
FAU - Lindner, Steffen N
AU  - Lindner SN
AUID- ORCID: 0000-0003-3226-3043
AD  - Max Planck Institute of Molecular Plant Physiology, Am Muhlenberg 1, 14476, 
      Potsdam, Germany. lindner@mpimp-golm.mpg.de.
FAU - Bar-Even, Arren
AU  - Bar-Even A
AUID- ORCID: 0000-0002-1039-4328
AD  - Max Planck Institute of Molecular Plant Physiology, Am Muhlenberg 1, 14476, 
      Potsdam, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201116
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (Sugars)
SB  - IM
MH  - Adaptation, Physiological
MH  - *Carbon Cycle
MH  - Computer Simulation
MH  - Escherichia coli/enzymology/*metabolism
MH  - Fermentation
MH  - Kinetics
MH  - Mutation/genetics
MH  - Oxidation-Reduction
MH  - Sugars/metabolism
PMC - PMC7669889
COIS- The authors declare no competing interests.
EDAT- 2020/11/18 06:00
MHDA- 2020/11/26 06:00
PMCR- 2020/11/16
CRDT- 2020/11/17 06:16
PHST- 2019/10/23 00:00 [received]
PHST- 2020/10/15 00:00 [accepted]
PHST- 2020/11/17 06:16 [entrez]
PHST- 2020/11/18 06:00 [pubmed]
PHST- 2020/11/26 06:00 [medline]
PHST- 2020/11/16 00:00 [pmc-release]
AID - 10.1038/s41467-020-19564-5 [pii]
AID - 19564 [pii]
AID - 10.1038/s41467-020-19564-5 [doi]
PST - epublish
SO  - Nat Commun. 2020 Nov 16;11(1):5812. doi: 10.1038/s41467-020-19564-5.