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雷公藤红素:从分离到生物技术生产再到抗肥胖药物开发的百年历程。

Celastrol: A century-long journey from the isolation to the biotechnological production and the development of an antiobesity drug.

机构信息

Biochemical Engineering Group, Plant Biochemistry Section, Department of Plant and Environment Sciences, Faculty of Science, University of Copenhagen, Thorvaldsensvej 40, 1871 Frederiksberg C, Denmark.

Biochemical Engineering Group, Plant Biochemistry Section, Department of Plant and Environment Sciences, Faculty of Science, University of Copenhagen, Thorvaldsensvej 40, 1871 Frederiksberg C, Denmark.

出版信息

Curr Opin Plant Biol. 2024 Oct;81:102615. doi: 10.1016/j.pbi.2024.102615. Epub 2024 Aug 10.

DOI:10.1016/j.pbi.2024.102615
PMID:39128271
Abstract

Celastrol, a triterpenoid found in the root of the traditional medicinal plant Tripterygium wilfordii, is a potent anti-inflammatory and antiobesity agent. However, pharmacological exploitation of celastrol has been hindered by the limited accessibility of plant material, the co-existence of other toxic compounds in the same plant tissue, and the lack of an efficient chemical synthesis method. In this review, we highlight recent progress in elucidating celastrol biosynthesis and discuss how this knowledge can facilitate its scalable bioproduction using cell factories and its further development as an antiobesity and anti-inflammatory drug.

摘要

雷公藤红素是从传统药用植物雷公藤的根部提取的一种三萜类化合物,具有很强的抗炎和抗肥胖作用。然而,雷公藤红素的药理学开发受到植物材料获取有限、同一植物组织中存在其他有毒化合物以及缺乏有效化学合成方法的限制。在这篇综述中,我们强调了阐明雷公藤红素生物合成的最新进展,并讨论了如何利用细胞工厂进行规模化生物生产以及将其进一步开发为抗肥胖和抗炎药物。

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Celastrol: A century-long journey from the isolation to the biotechnological production and the development of an antiobesity drug.雷公藤红素:从分离到生物技术生产再到抗肥胖药物开发的百年历程。
Curr Opin Plant Biol. 2024 Oct;81:102615. doi: 10.1016/j.pbi.2024.102615. Epub 2024 Aug 10.
2
Integrating pathway elucidation with yeast engineering to produce polpunonic acid the precursor of the anti-obesity agent celastrol.将通路阐明与酵母工程相结合,生产具有减肥作用的 celastrol 前体物——polpunonic 酸。
Microb Cell Fact. 2020 Jan 28;19(1):15. doi: 10.1186/s12934-020-1284-9.
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Biosynthesis and biotechnological production of the anti-obesity agent celastrol.肥胖症治疗剂雷公藤红素的生物合成与生物技术生产。
Nat Chem. 2023 Sep;15(9):1236-1246. doi: 10.1038/s41557-023-01245-7. Epub 2023 Jun 26.
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Identification of a cytochrome P450 from Tripterygium hypoglaucum (Levl.) Hutch that catalyzes polpunonic acid formation in celastrol biosynthesis.鉴定雷公藤中的细胞色素 P450 能够催化雷公藤红素生物合成中的雷公藤酮酸形成。
Chin J Nat Med. 2022 Sep;20(9):691-700. doi: 10.1016/S1875-5364(22)60205-X.
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Biosynthesis, total synthesis, structural modifications, bioactivity, and mechanism of action of the quinone-methide triterpenoid celastrol.昆诺酮型三萜化合物雷公藤红素的生物合成、全合成、结构修饰、生物活性及作用机制。
Med Res Rev. 2021 Mar;41(2):1022-1060. doi: 10.1002/med.21751. Epub 2020 Nov 10.
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Friedelane-type triterpene cyclase in celastrol biosynthesis from Tripterygium wilfordii and its application for triterpenes biosynthesis in yeast.卫矛醇生物合成中 Friedelane 型三萜环化酶及其在酵母中三萜生物合成的应用。
New Phytol. 2019 Jul;223(2):722-735. doi: 10.1111/nph.15809. Epub 2019 Apr 19.
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Cytochrome P450 catalyses the 29-carboxyl group formation of celastrol.细胞色素 P450 催化雷公藤红素的 29-羧基形成。
Phytochemistry. 2021 Oct;190:112868. doi: 10.1016/j.phytochem.2021.112868. Epub 2021 Jul 15.
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Overexpression and RNAi-mediated downregulation of TwIDI regulates triptolide and celastrol accumulation in Tripterygium wilfordii.TwIDI 的过表达和 RNAi 介导的下调调控雷公藤红素和雷公藤红素在雷公藤中的积累。
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Potential medicinal value of celastrol and its synthesized analogues for central nervous system diseases.藜芦碱及其合成类似物在中枢神经系统疾病方面的潜在药用价值。
Biomed Pharmacother. 2021 Jul;139:111551. doi: 10.1016/j.biopha.2021.111551. Epub 2021 Apr 14.
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The MVA pathway genes expressions and accumulation of celastrol in Tripterygium wilfordii suspension cells in response to methyl jasmonate treatment.响应茉莉酸甲酯处理的雷公藤悬浮细胞中MVA途径基因表达及雷公藤红素的积累
J Asian Nat Prod Res. 2016 Jul;18(7):619-28. doi: 10.1080/10286020.2015.1134504. Epub 2016 Jan 19.

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Effects of Celastrol-Enriched Peanuts on Metabolic Health and the Development of Atherosclerosis.
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