Engineering a functional 1-deoxy-D-xylulose 5-phosphate (DXP) pathway in Saccharomyces cerevisiae
| Autor: | Eugene Antipov, Lishan Zhao, Peter Jackson, Pinghua Liu, Sheela Muley, Jack D. Newman, Kevin L. Dietzel, Jeremy LaBarge, James Kirby, Gale Wichmann, Jay D. Keasling, Shayin S. Gottlieb, Sara P. Gaucher, Nathan A. Moss, Rossana Chan, Edward E. K. Baidoo, Kristy Michelle Hawkins, Tina Mahatdejkul |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Saccharomyces cerevisiae Bioengineering yeast Applied Microbiology and Biotechnology Article Industrial Biotechnology Metabolic engineering 03 medical and health sciences Synthetic biology chemistry.chemical_compound Glyceraldehyde terpene Pentosephosphates 030102 biochemistry & molecular biology biology Terpenes organic chemicals biology.organism_classification Terpenoid Yeast Cytosol 030104 developmental biology Metabolic Engineering Biochemistry chemistry Mevalonate pathway MEP pathway Biotechnology |
| Zdroj: | Kirby, J; Dietzel, KL; Wichmann, G; Chan, R; Antipov, E; Moss, N; et al.(2016). Engineering a functional 1-deoxy-D-xylulose 5-phosphate (DXP) pathway in Saccharomyces cerevisiae. Metabolic Engineering, 38, 494-503. doi: 10.1016/j.ymben.2016.10.017. UC Berkeley: Retrieved from: http://www.escholarship.org/uc/item/38t56316 |
| ISSN: | 1096-7176 |
| Popis: | © 2016 International Metabolic Engineering Society 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. |
| Databáze: | OpenAIRE |
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