新型靶向化合物——植物大麻素的生物合成途径及 研究进展
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国家自然科学基金 (No. 21807011),福建省自然科学基金 (No. 2018J01673),福建省省属高校科研专项 (No. JK2017012) 资助。


New targeted compounds—biosynthesis of phytocannabinoids
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National Natural Science Foundation of China (No. 21807011), Natural Science Foundation of Fujian Province, China (No. 2018J01673), Foundation of Fujian Educational Committee, China (No. JK2017012).

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    摘要:

    植物大麻素是具有生物活性的一系列萜类化合物的总称,被认为是大麻的专有成分。具有主要药理活性的植物大麻素为Δ9-四氢大麻酚 (Δ9-tetrahydrocannabinol,Δ9-THC) 和大麻二酚 (Cannabidiol,CBD),均以内源性大麻素受体为靶点,通过激活内源性大麻素系统而参与人体许多生理病理过程,具有广泛的治疗潜力。目前,Δ9-THC、CBD及其类似物或组合制剂,已用于治疗癫痫、癌症化疗患者的呕吐、多发性硬化症痉挛和缓解神经性疼痛以及晚期癌症患者的疼痛。随着对Δ9-THC和CBD应用价值的深度发掘和药用标准化制剂需求量增加,Δ9-THC和CBD在制药工业中实现规模化生产迫在眉睫。通过综述近年来植物大麻素的药理学研究进展,植物大麻素生物合成途径和关键酶的作用机制以及制药工业中植物大麻素的生产策略,旨在探索利用合成生物学技术解决植物大麻素药源问题的潜力,为合成大麻素的微生物工程研发提供理论基础,促进药用大麻素的规模化生产。

    Abstract:

    Phytocannabinoids are bioactive terpenoids that are exclusive to Cannabis sativa L. The main pharmacologically active phytocannabinoids are Δ9-tetrahydrocannabinol and cannabidiol, both target endogenous cannabinoid receptors. Δ9-tetrahydrocannabinol and cannabidiol have extensive therapeutic potential due to their participation in many physiological and pathological processes in human body by activating the endocannabinoid system. At present, Δ9-tetrahydrocannabinol, cannabidiol and their analogues or combination preparations are used to treat epilepsy, vomiting in patients with cancer chemotherapy, spasticity in multiple sclerosis and relieve neuropathic pain and pain in patients with advanced cancer. With the further exploration of the application value of Δ9-tetrahydrocannabinol and cannabidiol as well as the increasing demand for standardization of pharmaceutical preparations, it is imminent to achieve large-scale production of Δ9-tetrahydrocannabinol and cannabidiol in the pharmaceutical industry. In this article, pharmacological research progress of phytocannabinoids in recent years, biosynthetic pathways of phytocannabinoids and the mechanism of key enzymes as well as various product development strategies of cannabinoids in pharmaceutical industry are reviewed. By exploring the potential of synthetic biology as an alternative strategy for the source of phytocannabinoids, it will provide a theoretical basis for the research and development of microbial engineering for cannabinoids synthesis, and promote the large-scale production of medicinal cannabinoids.

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高萍,陈宇娴,柯崇榕,杨欣伟,黄建忠. 新型靶向化合物——植物大麻素的生物合成途径及 研究进展[J]. 生物工程学报, 2021, 37(6): 1968-1985

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  • 收稿日期:2020-07-24
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  • 在线发布日期: 2021-06-24
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