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在多功能酵母表达平台中通过多基因途径的工程化实现吲哚葡糖苷的微生物生产。

Microbial production of indolylglucosinolate through engineering of a multi-gene pathway in a versatile yeast expression platform.

机构信息

University of Copenhagen, Faculty of Life Sciences, Department of Plant Biology and Biotechnology, Molecular Plant Biology, VKR Research Centre for Pro-Active Plants, 40 Thorvaldsensvej, Frederiksberg C, Copenhagen, Denmark.

出版信息

Metab Eng. 2012 Mar;14(2):104-11. doi: 10.1016/j.ymben.2012.01.006. Epub 2012 Feb 4.

DOI:10.1016/j.ymben.2012.01.006
PMID:22326477
Abstract

Epidemiological studies have shown that consumption of cruciferous vegetables, such as, broccoli and cabbages, is associated with a reduced risk of developing cancer. This phenomenon has been attributed to specific glucosinolates among the ~30 glucosinolates that are typically present as natural products characteristic of cruciferous plants. Accordingly, there has been a strong interest to produce these compounds in microbial cell factories as it will allow production of selected beneficial glucosinolates. We have developed a versatile platform for stable expression of multi-gene pathways in the yeast, Saccharomyces cerevisiae. Introduction of the seven-step pathway of indolylglucosinolate from Arabidopsis thaliana to yeast resulted in the first successful production of glucosinolates in a microbial host. The production of indolylglucosinolate was further optimized by substituting supporting endogenous yeast activities with plant-derived enzymes. Production of indolylglucosinolate serves as a proof-of-concept for our expression platform, and provides a basis for large-scale microbial production of specific glucosinolates for the benefit of human health.

摘要

流行病学研究表明,食用十字花科蔬菜,如西兰花和卷心菜,与降低癌症风险有关。这种现象归因于十字花科植物中存在的约 30 种硫代葡萄糖苷中的特定硫代葡萄糖苷。因此,人们强烈希望在微生物细胞工厂中生产这些化合物,因为这将允许生产选定的有益硫代葡萄糖苷。我们已经开发了一种用于在酵母酿酒酵母中稳定表达多基因途径的多功能平台。向酵母中引入来自拟南芥的吲哚葡萄糖苷的七步途径,首次成功地在微生物宿主中生产了硫代葡萄糖苷。通过用植物来源的酶替代支持内源性酵母活性来进一步优化吲哚葡萄糖苷的生产。吲哚葡萄糖苷的生产为我们的表达平台提供了概念验证,并为大规模微生物生产特定的硫代葡萄糖苷以造福人类健康提供了基础。

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