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J Biotechnol. 2014 Sep 30;186:128-36. doi: 10.1016/j.jbiotec.2014.06.024. Epub 2014 Jul 9.

Enhanced isoprene biosynthesis in Saccharomyces cerevisiae by engineering of the native acetyl-CoA and mevalonic acid pathways with a push-pull-restrain strategy.

Lv X1, Xie W1, Lu W1, Guo F1, Gu J1, Yu H1, Ye L2.

Author information

1
Key Laboratory of Biomass Chemical Engineering of Ministry of Education, Department of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, PR China.
2
Key Laboratory of Biomass Chemical Engineering of Ministry of Education, Department of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, PR China. Electronic address: yelidan@zju.edu.cn.

Abstract

To explore the capacity of isoprene production in Saccharomyces cerevisiae, a rational push-pull-restrain strategy was proposed to engineer the mevalonic acid (MVA) and acetyl-CoA pathways. The strategy can be decomposed into the up-regulation of precursor supply in the acetyl-CoA module and the MVA pathway (push-strategy), increase of the isoprene branch flux (pull-strategy), and down-regulation of the competing pathway (restrain-strategy). Furthermore, to reduce the production cost arising from galactose addition and meanwhile maintain the high expression of Gal promoters, the galactose regulatory network was modulated by Gal80p deletion. Finally, the engineered strain YXM10-ispS-ispS could accumulate up to 37 mg/L isoprene (about 782-fold increase compared to the parental strain) under aerobic conditions with glycerol-sucrose as carbon source. In this way, a new potential platform for isoprene production was established via metabolic engineering of the yeast native pathways.

KEYWORDS:

Acetyl-CoA supply; Isoprene; Mevalonic acid pathway; Push-pull-restrain strategy; Saccharomyces cerevisiae

PMID:
25016205
DOI:
10.1016/j.jbiotec.2014.06.024
[Indexed for MEDLINE]
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