Open Access

Proceedings of the National Academy of Sciences (PNAS)

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}

Hide authors affiliations Show authors affiliations: 19 affiliations

Department of Chemistry,

Department of Biochemistry and Molecular Medicine, and

Genome Center, University of California, Davis, CA 95616; |

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; |

⁹

Department of Plant Sciences, Weizmann Institute of Sciences, Rehovot 76100, Israel; |

¹⁰

Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109; |

¹¹

Biomass Science and Conversion Technology, Sandia National Laboratories, Livermore, CA 94550; |

¹²

Graduate Program in Molecular and Cellular Biology,

¹³

Howard Hughes Medical Institute, |

¹⁴

Department of Energy, Joint Genome Institute, Lawrence National Berkeley Laboratory, Walnut Creek, CA 94598;

Lawrence Berkeley National Laboratory

Joint Genome Institute

¹⁵

Department of Chemistry, and

¹⁶

QB3 Institute, University of California, Berkeley, CA 94270; |

¹⁷

Synthetic Biology Engineering Research Center, Emeryville, CA 94608; and |

¹⁸

Physical Bioscience Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94270 |

¹⁹

Department of Microbiology, University of Washington, Seattle, WA 98195; |

Publication type: Journal Article

Publication date: 2015-03-09

Proceedings of the National Academy of Sciences (PNAS)

Proceedings of the National Academy of Sciences of the United States of America

scimago Q1

wos Q1

SJR: 3.414

CiteScore: 16.5

Impact factor: 9.1

ISSN: 00278424, 10916490

DOI: 10.1073/pnas.1500545112

Copy DOI

PubMed ID: 25775555

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.

Found

2 citations

Wohlgemuth Roland

PhD in Chemistry, professor

65 publications, 1 594 citations, 187 reviews

h-index: 18

Lodz University of Technology

Industrial biotechnology

Metabolomics

1 citation

Malyshev Alexander

5 publications, 35 citations

h-index: 3

Lomonosov Moscow State University

Dukhov Research Institute of Automatics

Herzen Moscow Oncology Research Institute

Research interests

Computational chemistry

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361

Cite this

GOST |

Cite this

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

PMID - 25775555

SN - 0027-8424

SN - 1091-6490

ER -

BibTex |

Cite this

BibTex (up to 50 authors) 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.

Publisher

Proceedings of the National Academy of Sciences (PNAS)

Journal

Proceedings of the National Academy of Sciences of the United States of America

scimago Q1

wos Q1

SJR

3.414

CiteScore

16.5

Impact factor

9.1

ISSN

00278424 (Print)

10916490 (Electronic)