Engineering yeast for high-level production of stilbenoid antioxidants.
Engineering yeast for high-level production of stilbenoid antioxidants.
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DOI：
10.1038/srep36827
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发表时间：
2016-11-11
影响因子：
4.6
通讯作者：
Nielsen J
中科院分区：
文献类型：
--
作者：
Li M;Schneider K;Kristensen M;Borodina I;Nielsen J
芪类化合物，包括白藜芦醇及其甲基化衍生物，是天然有效的抗氧化剂，由一些植物产生的微量防御化合物。从天然来源中提取芪类化合物是昂贵的，因为它们的丰度低，并且植物的可用性往往有限。在这里，我们设计的酵母酿酒酵母生产芪类化合物的简单的矿物介质通常用于工业生产。我们应用了一种拉-推-阻断的菌株工程策略，包括白藜芦醇生物合成途径的过表达，优化电子转移到细胞色素P450单加氧酶，增加前体供应，减少途径中间体降解。最终菌株的补料分批发酵导致800 mg l-1白藜芦醇的最终滴度，这是迄今为止报道的从葡萄糖生产白藜芦醇的最高滴度。我们进一步将异源甲基转移酶整合到白藜芦醇平台菌株中，并由此首次证明了从葡萄糖从头生物合成在人体中具有更好稳定性和摄取的松芪和紫檀芪。
Stilbenoids, including resveratrol and its methylated derivatives, are natural potent antioxidants, produced by some plants in trace amounts as defense compounds. Extraction of stilbenoids from natural sources is costly due to their low abundance and often limited availability of the plant. Here we engineered the yeast Saccharomyces cerevisiae for production of stilbenoids on a simple mineral medium typically used for industrial production. We applied a pull-push-block strain engineering strategy that included overexpression of the resveratrol biosynthesis pathway, optimization of the electron transfer to the cytochrome P450 monooxygenase, increase of the precursors supply, and decrease of the pathway intermediates degradation. Fed-batch fermentation of the final strain resulted in a final titer of 800 mg l−1 resveratrol, which is by far the highest titer reported to date for production of resveratrol from glucose. We further integrated heterologous methyltransferases into the resveratrol platform strain and hereby demonstrated for the first time de novo biosynthesis of pinostilbene and pterostilbene, which have better stability and uptake in the human body, from glucose.
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影响因子：
3.8
作者：
Jeong YJ;Woo SG;An CH;Jeong HJ;Hong YS;Kim YM;Ryu YB;Rho MC;Lee WS;Kim CY
通讯作者：
Kim CY
影响因子：
3.2
作者：
Jensen NB;Strucko T;Kildegaard KR;David F;Maury J;Mortensen UH;Forster J;Nielsen J;Borodina I
通讯作者：
Borodina I
DOI：
10.1039/9781849737579-00058
发表时间：
2013-01-01
期刊：
NATURAL PRODUCT EXTRACTION: PRINCIPLES AND APPLICATIONS
影响因子：
--
作者：
Palma, M.;Barbero, G. F.;Meireles, M. A. A.
通讯作者：
Meireles, M. A. A.
DOI：
10.1016/j.bbrc.2009.04.100
发表时间：
2009-06-26
影响因子：
3.1
作者：
Roy, Preeti;Kalra, Neetu;Shukla, Yogeshwer
通讯作者：
Shukla, Yogeshwer
影响因子：
7.2
作者：
Remsberg, Connie M.;Yanez, Jaime A.;Davies, Neal M.
通讯作者：
Davies, Neal M.