Metabolic engineering of Saccharomyces cerevisiae for the biotechnological production of succinic acid

被引:174
作者
Raab, Andreas M. [1 ,2 ]
Gebhardt, Gabi [3 ]
Bolotina, Natalia [2 ]
Weuster-Botz, Dirk [3 ]
Lang, Christine [1 ,2 ]
机构
[1] Berlin Univ Technol, Inst Biotechnol, Dept Genet & Microbiol, D-13355 Berlin, Germany
[2] ORGANOBALANCE GmbH, D-13355 Berlin, Germany
[3] Tech Univ Munich, Inst Biochem Engn, D-85748 Garching, Germany
关键词
Yeast; Saccharomyces cerevisiae; Succinic acid; Metabolic engineering; Production; MANNHEIMIA-SUCCINICIPRODUCENS LPK7; ESCHERICHIA-COLI; ISOCITRATE DEHYDROGENASE; GENE DISRUPTION; SAKE YEAST; CORYNEBACTERIUM-GLUTAMICUM; UBIQUINONE OXIDOREDUCTASE; ORGANIC-ACIDS; BOVINE RUMEN; EXPRESSION;
D O I
10.1016/j.ymben.2010.08.005
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
The production of bio-based succinic acid is receiving great attention, and several predominantly prokaryotic organisms have been evaluated for this purpose. In this study we report on the suitability of the highly acid- and osmotolerant yeast Saccharomyces cerevisiae as a succinic acid production host. We implemented a metabolic engineering strategy for the oxidative production of succinic acid in yeast by deletion of the genes SDH1, SDH2, IDH1 and IDP1. The engineered strains harbor a TCA cycle that is completely interrupted after the intermediates isocitrate and succinate. The strains show no serious growth constraints on glucose. In glucose-grown shake flask cultures, the quadruple deletion strain Delta sdh1 Delta sdh2 Delta idh1 Delta idp1 produces succinic acid at a titer of 3.62 gL(-1) (factor 4.8 compared to wild-type) at a yield of 0.11 mol (mol glucose)(-1). Succinic acid is not accumulated intracellularly. This makes the yeast S. cerevisiae a suitable and promising candidate for the biotechnological production of succinic acid on an industrial scale. (C) 2010 Elsevier Inc. All rights reserved.
引用
收藏
页码:518 / 525
页数:8
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