重构生物合成基因簇用于微生物天然产物的异源生产。
Refactoring biosynthetic gene clusters for heterologous production of microbial natural products.
作者信息
Li Lei, Maclntyre Logan W, Brady Sean F
机构信息
Laboratory of Genetically Encoded Small Molecules, The Rockefeller University, 1230 York Avenue, New York, NY 10065, United States.
Laboratory of Genetically Encoded Small Molecules, The Rockefeller University, 1230 York Avenue, New York, NY 10065, United States.
出版信息
Curr Opin Biotechnol. 2021 Jun;69:145-152. doi: 10.1016/j.copbio.2020.12.011. Epub 2021 Jan 18.
Abstract
Microbial natural products (NPs) are of paramount importance in human medicine, animal health and plant crop protection. Large-scale microbial genome and metagenomic mining has revealed tremendous biosynthetic potential to produce new NPs. However a majority of NP biosynthetic gene clusters (BGCs) are functionally inaccessible under standard laboratory conditions. BGC refactoring and heterologous expression provide a promising synthetic biology approach to NP discovery, yield optimization and combinatorial biosynthesis studies. In this review, we summarize the recent advances pertaining to the heterologous production of bacterial and fungal NPs, with an emphasis on next-generation transcriptional regulatory modules, novel BGC refactoring techniques and optimized heterologous hosts.
摘要
微生物天然产物在人类医学、动物健康和植物作物保护中至关重要。大规模的微生物基因组和宏基因组挖掘揭示了产生新天然产物的巨大生物合成潜力。然而，在标准实验室条件下，大多数天然产物生物合成基因簇（BGCs）在功能上难以利用。BGC重构和异源表达为天然产物发现、产量优化和组合生物合成研究提供了一种有前景的合成生物学方法。在本综述中，我们总结了细菌和真菌天然产物异源生产的最新进展，重点关注下一代转录调控模块、新型BGC重构技术和优化的异源宿主。
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