Zhang Yifeng, Ma Lin, Su Ping, Huang Luqi, Gao Wei
Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
School of Traditional Chinese Medicine, Capital Medical University, Beijing, China.
Crit Rev Biotechnol. 2023 Feb;43(1):1-21. doi: 10.1080/07388551.2021.2003292. Epub 2021 Dec 5.
As the largest family of natural products, terpenoids play valuable roles in medicine, agriculture, cosmetics and food. However, the traditional methods that rely on direct extraction from the original plants not only produce low yields, but also result in waste of resources, and are not applicable at all to endangered species. Modern heterologous biosynthesis is considered a promising, efficient, and sustainable production method, but it relies on the premise of a complete analysis of the biosynthetic pathway of terpenoids, especially the functionalization processes involving downstream cytochrome P450s. In this review, we systematically introduce the biotech approaches used to discover and characterize plant terpenoid-related P450s in recent years. In addition, we propose corresponding metabolic engineering approaches to increase the effective expression of P450 and improve the yield of terpenoids, and also elaborate on metabolic engineering strategies and examples of heterologous biosynthesis of terpenoids in and plant hosts. Finally, we provide perspectives for the biotech approaches to be developed for future research on terpenoid-related P450.
作为最大的天然产物家族,萜类化合物在医药、农业、化妆品和食品领域发挥着重要作用。然而,传统的从原始植物中直接提取的方法不仅产量低,还会导致资源浪费,并且完全不适用于濒危物种。现代异源生物合成被认为是一种有前景、高效且可持续的生产方法,但它依赖于对萜类化合物生物合成途径进行全面分析的前提,尤其是涉及下游细胞色素P450的功能化过程。在本综述中,我们系统地介绍了近年来用于发现和表征植物萜类化合物相关P450的生物技术方法。此外,我们提出了相应的代谢工程方法来提高P450的有效表达并提高萜类化合物的产量,还阐述了在微生物和植物宿主中萜类化合物异源生物合成的代谢工程策略及实例。最后,我们为未来萜类化合物相关P450研究中有待开发的生物技术方法提供了展望。