Engineering a functional 1-deoxy-D-xylulose 5-phosphate (DXP) pathway in Saccharomyces cerevisiae |
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| Affiliation: | 1. Amyris, Inc., 5885 Hollis Street, Suite 100, Emeryville, CA 94608, USA;2. California Institute of Quantitative Biosciences (QB3), University of California, Berkeley, CA 94702, USA;3. Joint BioEnergy Institute, Emeryville, CA 94608, USA;4. Department of Chemistry, Boston University, Boston, MA 02215, USA;5. Departments of Chemical & Biomolecular Engineering and of Bioengineering, University of California, Berkeley, CA 94702, USA;6. Biological Systems & Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94702, USA;7. Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kogle Allé, DK2970 Hørsholm, Denmark;1. Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117585, Singapore;2. Temasek Laboratories, National University of Singapore, T-Lab Building 5A, Engineering Drive 1, Singapore 117411, Singapore;3. Singapore Institute of Technology, 10 Dover Drive, Singapore 138683, Singapore;1. Joint BioEnergy Institute, 5885 Hollis Street, 4th Floor, Emeryville, CA 94608, United States;2. Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, United States;3. Joint Genome Institute, Walnut Creek, CA 94598, United States;4. QB3 Institute, University of California-Berkeley, 5885 Hollis Street, 4th Floor, Emeryville, CA 94608, United States;5. Synthetic Biology Engineering Research Center, University of California, Berkeley, CA 94720, United States;6. Department of Chemical & Biomolecular Engineering, Department of Bioengineering, University of California, Berkeley, CA 94720, United States;1. DOE Joint BioEnergy Institute, 5885 Hollis St., Emeryville, CA 94608, United States;2. Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, United States;3. California Institute of Quantitative Biosciences (QB3), University of California, Berkeley, CA 94720, United States;4. National Bioenergy Center, National Renewable Energy Laboratory, Golden, CO 80401, United States;5. Biosciences Center, National Renewable Energy Laboratory, Golden, CO 80401, United States;6. Department of Chemical and Biomolecular Engineering, University of California, Berkeley, CA 94720, United States;7. Department of Bioengineering, University of California, Berkeley, CA 94720, United States;8. The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Building 220, Kemitorvet, 2800 Kgs, Lyngby, Denmark;9. Center for Synthetic Biochemistry, Institute for Synthetic Biology, Shenzhen Institutes for Advanced Technologies, Shenzhen, China |
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| Abstract: | Isoprenoids are used in many commercial applications and much work has gone into engineering microbial hosts for their production. Isoprenoids are produced either from acetyl-CoA via the mevalonate pathway or from pyruvate and glyceraldehyde 3-phosphate via the 1-deoxy-D-xylulose 5-phosphate (DXP) pathway. Saccharomyces cerevisiae exclusively utilizes the mevalonate pathway to synthesize native isoprenoids and in fact the alternative DXP pathway has never been found or successfully reconstructed in the eukaryotic cytosol. There are, however, several advantages to isoprenoid synthesis via the DXP pathway, such as a higher theoretical yield, and it has long been a goal to transplant the pathway into yeast. In this work, we investigate and address barriers to DXP pathway functionality in S. cerevisiae using a combination of synthetic biology, biochemistry and metabolomics. We report, for the first time, functional expression of the DXP pathway in S. cerevisiae. Under low aeration conditions, an engineered strain relying solely on the DXP pathway for isoprenoid biosynthesis achieved an endpoint biomass 80% of that of the same strain using the mevalonate pathway. |
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| Keywords: | MEP pathway yeast metabolic engineering terpene |
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