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酵母代谢工程——靶向固醇代谢和萜烯形成。

Yeast metabolic engineering--targeting sterol metabolism and terpenoid formation.

机构信息

ACIB-Austrian Centre of Industrial Biotechnology, Graz, Austria.

出版信息

Prog Lipid Res. 2013 Jul;52(3):277-93. doi: 10.1016/j.plipres.2013.03.001. Epub 2013 Apr 6.

Abstract

Terpenoids comprise various structures conferring versatile functions to eukaryotes, for example in the form of prenyl-anchors they attach proteins to membranes. The physiology of eukaryotic membranes is fine-tuned by another terpenoid class, namely sterols. Evidence is accumulating that numerous membrane proteins require specific sterol structural features for function. Moreover, sterols are intermediates in the synthesis of steroids serving as hormones in higher eukaryotes. Like steroids many compounds of the terpenoid family do not contribute to membrane architecture, but serve as signalling, protective or attractant/repellent molecules. Particularly plants have developed a plenitude of terpenoid biosynthetic routes branching off early in the sterol biosynthesis pathway and, thereby, forming one of the largest groups of naturally occurring organic compounds. Many of these aromatic and volatile molecules are interesting for industrial application ranging from foods to pharmaceuticals. Combining the fortunate situation that sterol biosynthesis is highly conserved in eukaryotes with the amenability of yeasts to genetic and metabolic engineering, basically all naturally occurring terpenoids might be produced involving yeasts. Such engineered yeasts are useful for the study of biological functions and molecular interactions of terpenoids as well as for the large-scale production of high-value compounds, which are unavailable in sufficient amounts from natural sources due to their low abundance.

摘要

萜类化合物具有多种结构,赋予真核生物多种功能,例如通过 prenyl-anchor 将蛋白质附着到膜上。真核生物膜的生理学通过另一类萜类化合物——固醇来精细调节。有证据表明,许多膜蛋白需要特定的固醇结构特征才能发挥功能。此外,固醇是合成类固醇的中间体,类固醇在高等真核生物中作为激素发挥作用。与类固醇一样,萜类化合物家族的许多化合物并不参与膜结构,但作为信号、保护或吸引/排斥分子发挥作用。特别是植物已经开发出了大量的萜类生物合成途径,这些途径在固醇生物合成途径的早期就分支出来,从而形成了最大的天然有机化合物群体之一。这些芳香族和挥发性分子中的许多都因具有工业应用价值而受到关注,从食品到制药等领域都有涉及。结合固醇生物合成在真核生物中高度保守的有利情况,以及酵母对遗传和代谢工程的适用性,基本上所有天然萜类化合物都可以通过酵母来生产。这些经过工程改造的酵母可用于研究萜类化合物的生物学功能和分子相互作用,以及大规模生产高价值化合物,由于其含量低,从天然来源获得这些化合物的数量是不够的。

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