Berlin University of Technology, Institute for Biotechnology, Department of Microbiology and Genetics, Gustav-Meyer-Allee 25, D-13355 Berlin, Germany.
Metab Eng. 2010 Nov;12(6):518-25. doi: 10.1016/j.ymben.2010.08.005. Epub 2010 Sep 18.
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 Δsdh1Δsdh2Δidh1Δidp1 produces succinic acid at a titer of 3.62 g L(-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.
生物基琥珀酸的生产受到了广泛关注，已经有几种主要的原核生物被评估用于该目的。在本研究中，我们报告了高度耐酸和耐渗酵母酿酒酵母（Saccharomyces cerevisiae）作为琥珀酸生产宿主的适用性。我们通过敲除 SDH1、SDH2、IDH1 和 IDP1 基因，实施了一种在酵母中进行氧化生产琥珀酸的代谢工程策略。经过改造的菌株的三羧酸循环在中间产物异柠檬酸和琥珀酸之后完全中断。这些菌株在葡萄糖上生长时没有明显的生长限制。在葡萄糖摇瓶培养中，四缺失株 Δsdh1Δsdh2Δidh1Δidp1 以 3.62 g L(-1) 的浓度（与野生型相比提高了 4.8 倍）和 0.11 mol (mol 葡萄糖)(-1) 的产率产生琥珀酸。琥珀酸不会在细胞内积累。这使得酵母酿酒酵母成为工业规模生物技术生产琥珀酸的合适且有前途的候选者。
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