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Proceedings of the National Academy of Sciences of the United States of America, volume 112, issue 12, pages 3704-3709

Computational protein design enables a novel one-carbon assimilation pathway

Justin B Siegel 1, 2, 3, 4, 5
Amanda Lee Smith 6
Sean Poust 7, 8
Adam J Wargacki 4
Arren Bar-Even 9
Catherine Louw 4
Betty W. Shen 10
Christopher B Eiben 4, 7, 8
Huu M. Tran 8, 11
Elad Noor 9
Jasmine L Gallaher 4
Jacob Bale 4, 12
Yasuo Yoshikuni 4, 13, 14
Michael H. Gelb 4, 15
Jay D. Keasling 7, 8, 16, 17, 18
Barry L Stoddard 10
Mary E. Lidstrom 6, 19
David Baker 4, 5, 13
1
 
Department of Chemistry,
2
 
Department of Biochemistry and Molecular Medicine, and
4
 
Department of Biochemistry and the Institute for Protein Design,
5
 
Biomolecular Structure and Design Program,
6
 
Department of Chemical Engineering,
7
 
Department of Chemical and Biomolecular Engineering and
8
 
Joint BioEnergy Institute, Emeryville, CA 94608;
12
 
Graduate Program in Molecular and Cellular Biology,
15
 
Department of Chemistry, and
17
 
Synthetic Biology Engineering Research Center, Emeryville, CA 94608; and
Publication typeJournal Article
Publication date2015-03-09
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor11.1
ISSN00278424, 10916490
Multidisciplinary
Abstract
Significance

This paper describes the development of a computationally designed enzyme that is the cornerstone of a novel metabolic pathway. This enzyme, formolase, performs a carboligation reaction, directly fixing one-carbon units into three-carbon units that feed into central metabolism. By combining formolase with several naturally occurring enzymes, we created a new carbon fixation pathway, the formolase pathway, which assimilates one-carbon units via formate. Unlike native carbon fixation pathways, this pathway is linear, not oxygen sensitive, and consists of a small number of thermodynamically favorable steps. We demonstrate in vitro pathway function as a proof of principle of how protein design in a pathway context can lead to new efficient metabolic pathways.

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GOST |
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GOST Copy
Siegel J. B. et al. Computational protein design enables a novel one-carbon assimilation pathway // Proceedings of the National Academy of Sciences of the United States of America. 2015. Vol. 112. No. 12. pp. 3704-3709.
GOST all authors (up to 50) Copy
Siegel J. B., Smith A. L., Poust S., Wargacki A. J., Bar-Even A., Louw C., Shen B. W., Eiben C. B., Tran H. M., Noor E., Gallaher J. L., Bale J., Yoshikuni Y., Gelb M. H., Keasling J. D., Stoddard B. L., Lidstrom M. E., Baker D. Computational protein design enables a novel one-carbon assimilation pathway // Proceedings of the National Academy of Sciences of the United States of America. 2015. Vol. 112. No. 12. pp. 3704-3709.
RIS |
Cite this
RIS Copy
TY - JOUR
DO - 10.1073/pnas.1500545112
UR - https://doi.org/10.1073/pnas.1500545112
TI - Computational protein design enables a novel one-carbon assimilation pathway
T2 - Proceedings of the National Academy of Sciences of the United States of America
AU - Siegel, Justin B
AU - Smith, Amanda Lee
AU - Poust, Sean
AU - Wargacki, Adam J
AU - Bar-Even, Arren
AU - Louw, Catherine
AU - Shen, Betty W.
AU - Eiben, Christopher B
AU - Tran, Huu M.
AU - Noor, Elad
AU - Gallaher, Jasmine L
AU - Bale, Jacob
AU - Yoshikuni, Yasuo
AU - Gelb, Michael H.
AU - Keasling, Jay D.
AU - Stoddard, Barry L
AU - Lidstrom, Mary E.
AU - Baker, David
PY - 2015
DA - 2015/03/09
PB - Proceedings of the National Academy of Sciences (PNAS)
SP - 3704-3709
IS - 12
VL - 112
SN - 0027-8424
SN - 1091-6490
ER -
BibTex |
Cite this
BibTex Copy
@article{2015_Siegel,
author = {Justin B Siegel and Amanda Lee Smith and Sean Poust and Adam J Wargacki and Arren Bar-Even and Catherine Louw and Betty W. Shen and Christopher B Eiben and Huu M. Tran and Elad Noor and Jasmine L Gallaher and Jacob Bale and Yasuo Yoshikuni and Michael H. Gelb and Jay D. Keasling and Barry L Stoddard and Mary E. Lidstrom and David Baker},
title = {Computational protein design enables a novel one-carbon assimilation pathway},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {2015},
volume = {112},
publisher = {Proceedings of the National Academy of Sciences (PNAS)},
month = {mar},
url = {https://doi.org/10.1073/pnas.1500545112},
number = {12},
pages = {3704--3709},
doi = {10.1073/pnas.1500545112}
}
MLA
Cite this
MLA Copy
Siegel, Justin B., et al. “Computational protein design enables a novel one-carbon assimilation pathway.” Proceedings of the National Academy of Sciences of the United States of America, vol. 112, no. 12, Mar. 2015, pp. 3704-3709. https://doi.org/10.1073/pnas.1500545112.
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