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酵母代谢工程在制药重要次生代谢产物生产中的应用。

Yeast metabolic engineering for the production of pharmaceutically important secondary metabolites.

机构信息

Campus of Korea Institute of Oriental Medicine, Korean Convergence Medicine Major, University of Science & Technology (UST), Daejeon, 34054, Republic of Korea.

Herbal Medicine Resources Research Center, Korea Institute of Oriental Medicine, 111 Geonjae-ro, Naju-si, 58245, Jeollanam-do, Republic of Korea.

出版信息

Appl Microbiol Biotechnol. 2020 Jun;104(11):4659-4674. doi: 10.1007/s00253-020-10587-y. Epub 2020 Apr 8.

Abstract

In the last few decades, there has been a rapid increase in the discovery of drugs from natural products, particularly secondary metabolites. Various efforts have been undertaken to enhance and optimize the production system of these secondary metabolites to meet the increasing global market demand. Recently, metabolic engineering has been used for the heterologous synthesis of secondary metabolites in the engineered yeast strains. Here, we highlight the recent advancements in the production of pharmaceutically important secondary metabolites in metabolically engineered yeast, such as Saccharomyces cerevisiae and Pichia pastoris. Furthermore, we also emphasize the important application of synthetic biology methods that are supported by state-of-the-art post-genomic tools to improve the efficiency and success rate of yeast metabolic engineering for the production of natural drugs. Metabolic engineering using yeast as a microbial host factory to produce pharmaceutically useful secondary metabolites is a very promising strategy, which can be used to support the industrial production system. KEY POINTS: •Next-generation sequencing application for genome mining of secondary metabolites •Various synthetic biology tools for yeast metabolic engineering construction •Examples of successfully produced medicinal secondary metabolites in engineered yeast.

摘要

在过去的几十年中,从天然产物中发现药物的数量迅速增加,特别是次生代谢物。为了满足不断增长的全球市场需求,人们已经做出了各种努力来增强和优化这些次生代谢物的生产系统。最近,代谢工程已被用于在工程酵母菌株中异源合成次生代谢物。在这里,我们重点介绍了代谢工程酵母(如酿酒酵母和巴斯德毕赤酵母)中生产具有重要药用价值的次生代谢物的最新进展。此外,我们还强调了合成生物学方法的重要应用,这些方法得到了最先进的后基因组工具的支持,可用于提高酵母代谢工程生产天然药物的效率和成功率。利用酵母作为微生物宿主工厂生产具有药用价值的次生代谢物的代谢工程是一种很有前途的策略,可以用于支持工业生产系统。 要点: •下一代测序技术在次生代谢产物的基因组挖掘中的应用 •用于酵母代谢工程构建的各种合成生物学工具 •在工程酵母中成功生产的药用次生代谢物的实例。

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