Engineering a functional 1-deoxy-D-xylulose 5-phosphate (DXP) pathway in Saccharomyces cerevisiae.
Engineering a functional 1-deoxy-D-xylulose 5-phosphate (DXP) pathway in Saccharomyces cerevisiae.
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DOI：
10.1016/j.ymben.2016.10.017
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发表时间：
2016-11
影响因子：
8.4
通讯作者：
Zhao L
中科院分区：
文献类型：
--
作者：
Kirby J;Dietzel KL;Wichmann G;Chan R;Antipov E;Moss N;Baidoo EEK;Jackson P;Gaucher SP;Gottlieb S;LaBarge J;Mahatdejkul T;Hawkins KM;Muley S;Newman JD;Liu P;Keasling JD;Zhao L
异戊二烯类化合物被用于许多商业用途，许多工作都被用于工程微生物宿主的生产。异戊二烯类化合物可以由乙酰辅酶A通过甲氧戊酸途径或丙酮酸和甘油醛3-磷酸通过1-脱氧-D-木糖-5-磷酸(DXP)途径生成。酿酒酵母只利用甲氧戊酸途径合成天然的异戊二烯类化合物，事实上，在真核细胞中还没有发现或成功地重建了替代的DXP途径。然而，通过DXP途径合成类异戊二烯有几个优点，例如更高的理论产率，长期以来，将该途径移植到酵母中一直是一个目标。在这项工作中，我们使用合成生物学、生物化学和代谢组学的组合来研究和解决酿酒酵母DXP途径功能的障碍。我们首次报道了DXP途径在酿酒酵母中的功能表达。在低曝气条件下，仅依靠DXP途径合成类异戊二烯的工程菌获得的终点生物量是使用甲氧戊酸途径的相同菌株的80%。
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.
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影响因子：
6.4
作者：
Gruchattka E;Hädicke O;Klamt S;Schütz V;Kayser O
通讯作者：
Kayser O
DOI：
10.1073/pnas.0705829104
发表时间：
2007-08-21
影响因子：
11.1
作者：
Loiseau, Laurent;Gerez, Catherine;Barras, Frederic
通讯作者：
Barras, Frederic
影响因子：
3.5
作者：
Maury, Jerome;Asadollahi, Mohammad A.;Nielsen, Jens
通讯作者：
Nielsen, Jens
影响因子：
6.6
作者：
Lill, Roland;Dutkiewicz, Rafal;Milhlenhoff, Ulrich
通讯作者：
Milhlenhoff, Ulrich
影响因子：
2.8
作者：
Artsatbanov, V. Yu.;Vostroknutova, G. N.;Kapreliants, A. S.
通讯作者：
Kapreliants, A. S.