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Proc Natl Acad Sci U S A. 2015 Mar 24;112(12):3704-9. doi: 10.1073/pnas.1500545112. Epub 2015 Mar 9.

Computational protein design enables a novel one-carbon assimilation pathway.

Author information

1
Department of Chemistry, Department of Biochemistry and Molecular Medicine, and Genome Center, University of California, Davis, CA 95616; Department of Biochemistry and the Institute for Protein Design, Biomolecular Structure and Design Program.
2
Department of Chemical Engineering.
3
Department of Chemical and Biomolecular Engineering and Joint BioEnergy Institute, Emeryville, CA 94608;
4
Department of Biochemistry and the Institute for Protein Design.
5
Department of Plant Sciences, Weizmann Institute of Sciences, Rehovot 76100, Israel;
6
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109;
7
Department of Biochemistry and the Institute for Protein Design, Department of Chemical and Biomolecular Engineering and Joint BioEnergy Institute, Emeryville, CA 94608;
8
Joint BioEnergy Institute, Emeryville, CA 94608; Biomass Science and Conversion Technology, Sandia National Laboratories, Livermore, CA 94550;
9
Department of Biochemistry and the Institute for Protein Design, Graduate Program in Molecular and Cellular Biology.
10
Department of Biochemistry and the Institute for Protein Design, Department of Energy, Joint Genome Institute, Lawrence National Berkeley Laboratory, Walnut Creek, CA 94598; Howard Hughes Medical Institute.
11
Department of Biochemistry and the Institute for Protein Design, Department of Chemistry, and.
12
Department of Chemical and Biomolecular Engineering and Joint BioEnergy Institute, Emeryville, CA 94608; QB3 Institute, University of California, Berkeley, CA 94270; Synthetic Biology Engineering Research Center, Emeryville, CA 94608; and Physical Bioscience Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94270.
13
Department of Chemical Engineering, Department of Microbiology, University of Washington, Seattle, WA 98195; lidstrom@u.washington.edu dabaker@uw.edu.
14
Department of Biochemistry and the Institute for Protein Design, Biomolecular Structure and Design Program, Howard Hughes Medical Institute, lidstrom@u.washington.edu dabaker@uw.edu.

Abstract

We describe a computationally designed enzyme, formolase (FLS), which catalyzes the carboligation of three one-carbon formaldehyde molecules into one three-carbon dihydroxyacetone molecule. The existence of FLS enables the design of a new carbon fixation pathway, the formolase pathway, consisting of a small number of thermodynamically favorable chemical transformations that convert formate into a three-carbon sugar in central metabolism. The formolase pathway is predicted to use carbon more efficiently and with less backward flux than any naturally occurring one-carbon assimilation pathway. When supplemented with enzymes carrying out the other steps in the pathway, FLS converts formate into dihydroxyacetone phosphate and other central metabolites in vitro. These results demonstrate how modern protein engineering and design tools can facilitate the construction of a completely new biosynthetic pathway.

KEYWORDS:

carbon fixation; computational protein design; pathway engineering

Comment in

PMID:
25775555
PMCID:
PMC4378393
DOI:
10.1073/pnas.1500545112
[Indexed for MEDLINE]
Free PMC Article

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