酵母中天然产物生产的先进策略
Advanced Strategies for Production of Natural Products in Yeast.
作者信息
Chen Ruibing, Yang Shan, Zhang Lei, Zhou Yongjin J
机构信息
Division of Biotechnology, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, China; Department of Pharmaceutical Botany, School of Pharmacy, Naval Medical University, Shanghai 200433, China.
Division of Biotechnology, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, China; University of Chinese Academy of Sciences, Beijing 100049, China.
出版信息
iScience. 2020 Mar 27;23(3):100879. doi: 10.1016/j.isci.2020.100879. Epub 2020 Feb 1.
Natural products account for more than 50% of all small-molecule pharmaceutical agents currently in clinical use. However, low availability often becomes problematic when a bioactive natural product is promising to become a pharmaceutical or leading compound. Advances in synthetic biology and metabolic engineering provide a feasible solution for sustainable supply of these compounds. In this review, we have summarized current progress in engineering yeast cell factories for production of natural products, including terpenoids, alkaloids, and phenylpropanoids. We then discuss advanced strategies in metabolic engineering at three different dimensions, including point, line, and plane (corresponding to the individual enzymes and cofactors, metabolic pathways, and the global cellular network). In particular, we comprehensively discuss how to engineer cofactor biosynthesis for enhancing the biosynthesis efficiency, other than the enzyme activity. Finally, current challenges and perspective are also discussed for future engineering direction.
天然产物占目前临床使用的所有小分子药物的50%以上。然而，当一种具有生物活性的天然产物有望成为药物或先导化合物时，其低可用性往往会成为问题。合成生物学和代谢工程的进展为这些化合物的可持续供应提供了可行的解决方案。在这篇综述中，我们总结了利用酵母细胞工厂生产天然产物（包括萜类化合物、生物碱和苯丙素类化合物）的当前进展。然后，我们从三个不同维度讨论代谢工程的先进策略，包括点、线、面（分别对应单个酶和辅因子、代谢途径以及全局细胞网络）。特别是，我们全面讨论了如何除了酶活性之外，通过工程化辅因子生物合成来提高生物合成效率。最后，还讨论了当前的挑战以及对未来工程方向的展望。
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