Biotransformation of celastrol to a novel, well-soluble, low-toxic and anti-oxidative celastrol-29-O-β-glucoside by Bacillus glycosyltransferases
Biotransformation of celastrol to a novel, well-soluble, low-toxic and anti-oxidative celastrol-29-O-β-glucoside by Bacillus glycosyltransferases
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DOI：
10.1016/j.jbiosc.2020.09.017
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发表时间：
2021-01-28
影响因子：
2.8
通讯作者：
Wu, Jiumn-Yih
中科院分区：
文献类型：
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作者：
Chang, Te-Sheng;Wang, Tzi-Yuan;Wu, Jiumn-Yih
南蛇藤酚是从雷公藤（Thunder god vine）的根提取物中分离的醌甲基化三萜类化合物。雷公藤红素具有多种生物活性，但其毒性强、难溶于水等特点限制了其临床应用。使用全细胞或纯化的酶来生物转化雷公藤红素以形成毒性较小且更可溶的衍生物已被证明是困难的，这是由于其有效的抗生素和酶缀合性质。本研究评价了四种芽孢杆菌属的糖基转移酶对雷公藤红素的生物转化，发现一种枯草芽孢杆菌的糖基转移酶（BsGT 110）对雷公藤红素具有显著的活性。经纯化后的生物转化代谢产物经质谱和核磁共振鉴定为雷公藤红素-29-O-β-葡萄糖苷。雷公藤红素-29-O-β-葡萄糖苷的水溶性比雷公藤红素高53倍以上，同时保持了雷公藤红素50%的自由基清除活性。当使用斑马鱼作为体内动物模型时，雷公藤红素-29-0-β-葡糖苷表现出比雷公藤红素低50倍的毒性。据我们所知，本研究不仅是描述雷公藤红素的生物转化的第一个报告，而且是第一个详细描述生物转化过程中产生的新化合物雷公藤红素-29-O-β-葡萄糖苷的报告。此外，雷公藤红素-29-O-β-葡萄糖苷由于其较高的水溶性和较低的毒性，可能成为未来药物应用的潜在候选者。(C)2020年，生物技术学会，日本。All rights reserved.
Celastrol is a quinone-methide triterpenoid isolated from the root extracts of Tripterygium wilfordii (Thunder god vine). Although celastrol possesses multiple bioactivities, the potent toxicity and rare solubility in water hinder its clinical application. Biotransformation of celastrol using either whole cells or purified enzymes to form less toxic and more soluble derivatives has been proven difficult due to its potent antibiotic and enzyme-conjugation property. The present study evaluated biotransformation of celastrol by four glycosyltransferases from Bacillus species and found one glycosyltransferase (BsGT110) from Bacillus subtilis with significant activity toward celastrol. The biotransformation metabolite was purified and identified as celastrol-29-O-beta-glucoside by mass and nuclear magnetic resonance spectroscopy. Celastrol-29-O-beta-glucoside showed over 53-fold higher water solubility than celastrol, while maintained 50% of the free radical scavenging activity of celastrol. When using zebrafish as the in vivo animal model, celastrol-29-O-beta-glucoside exhibited 50-fold less toxicity than celastrol. To our knowledge, the present study is not only the first report describing the biotransformation of celastrol, but also the first one detailing a new compound, celastrol-29-O-beta-glucoside, that is generated in the biotransformation process. Moreover, celastrol-29-O-beta-glucoside may serve as a potential candidate in the future medicine application due to its higher water solubility and lower toxicity. (C) 2020, The Society for Biotechnology, Japan. All rights reserved.