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Metab Eng. 2016 Nov;38:494-503. doi: 10.1016/j.ymben.2016.10.017. Epub 2016 Oct 27.

Engineering a functional 1-deoxy-D-xylulose 5-phosphate (DXP) pathway in Saccharomyces cerevisiae.

Author information

1
California Institute of Quantitative Biosciences (QB3), University of California, Berkeley, CA 94702, USA; Joint BioEnergy Institute, Emeryville, CA 94608, USA.
2
Amyris, Inc., 5885 Hollis Street, Suite 100, Emeryville, CA 94608, USA.
3
Joint BioEnergy Institute, Emeryville, CA 94608, USA.
4
Department of Chemistry, Boston University, Boston, MA 02215, USA.
5
California Institute of Quantitative Biosciences (QB3), University of California, Berkeley, CA 94702, USA; Joint BioEnergy Institute, Emeryville, CA 94608, USA; Departments of Chemical & Biomolecular Engineering and of Bioengineering, University of California, Berkeley, CA 94702, USA; Biological Systems & Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94702, USA; Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kogle Allé, DK2970 Hørsholm, Denmark.
6
Amyris, Inc., 5885 Hollis Street, Suite 100, Emeryville, CA 94608, USA. Electronic address: zhao@amyris.com.

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.

KEYWORDS:

MEP pathway; metabolic engineering; terpene; yeast

PMID:
27989805
PMCID:
PMC5718835
DOI:
10.1016/j.ymben.2016.10.017
[Indexed for MEDLINE]
Free PMC Article

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