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植物(三萜)类化合物的生物工程:从植物的代谢工程到体内和体外的合成生物学。

Bioengineering of plant (tri)terpenoids: from metabolic engineering of plants to synthetic biology in vivo and in vitro.

机构信息

Department of Plant Systems Biology, VIB, Technologiepark 927, B-9052, Gent, Belgium.

Department of Plant Biotechnology and Bioinformatics, Ghent University, Technologiepark 927, B-9052, Gent, Belgium.

出版信息

New Phytol. 2013 Oct;200(1):27-43. doi: 10.1111/nph.12325. Epub 2013 May 14.

DOI:10.1111/nph.12325
PMID:23668256
Abstract

Terpenoids constitute a large and diverse class of natural products that serve many functions in nature. Most of the tens of thousands of the discovered terpenoids are synthesized by plants, where they function as primary metabolites involved in growth and development, or as secondary metabolites that optimize the interaction between the plant and its environment. Several plant terpenoids are economically important molecules that serve many applications as pharmaceuticals, pesticides, etc. Major challenges for the commercialization of plant-derived terpenoids include their low production levels in planta and the continuous demand of industry for novel molecules with new or superior biological activities. Here, we highlight several synthetic biology methods to enhance and diversify the production of plant terpenoids, with a foresight towards triterpenoid engineering, the least engineered class of bioactive terpenoids. Increased or cheaper production of valuable triterpenoids may be obtained by 'classic' metabolic engineering of plants or by heterologous production of the compounds in other plants or microbes. Novel triterpenoid structures can be generated through combinatorial biosynthesis or directed enzyme evolution approaches. In its ultimate form, synthetic biology may lead to the production of large amounts of plant triterpenoids in in vitro systems or custom-designed artificial biological systems.

摘要

萜类化合物是一大类结构多样的天然产物,在自然界中具有多种功能。在已发现的数万种萜类化合物中,大多数是由植物合成的,它们作为初级代谢物参与生长和发育,或者作为次级代谢物优化植物与环境之间的相互作用。一些植物萜类化合物是具有经济重要性的分子,可应用于制药、农药等领域。植物来源的萜类化合物商业化面临的主要挑战包括其在植物体内的低产量和工业界对具有新的或优越生物活性的新型分子的持续需求。在这里,我们重点介绍了几种合成生物学方法来增强和多样化植物萜类化合物的生产,前瞻性地考虑了三萜类化合物的工程改造,这是生物活性萜类化合物中最少被工程改造的一类。通过对植物进行“经典”的代谢工程改造,或者在其他植物或微生物中异源生产这些化合物,可以获得有价值的三萜类化合物的产量增加或成本降低。通过组合生物合成或定向酶进化方法可以产生新型三萜类化合物结构。在其最终形式中,合成生物学可能导致在体外系统或定制设计的人工生物系统中大量生产植物三萜类化合物。

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