Biotransformation of celastrol to a novel, well-soluble, low-toxic and anti-oxidative celastrol-29-O-β-glucoside by Bacillus glycosyltransferases

Te Sheng Chang, Tzi Yuan Wang, Chien Min Chiang, Yu Ju Lin, Hui Lien Chen, Yu Wei Wu, Huei Ju Ting, Jiumn Yih Wu

Research output: Contribution to journalArticlepeer-review

Abstract

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-β-glucoside by mass and nuclear magnetic resonance spectroscopy. Celastrol-29-O-β-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-β-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-β-glucoside, that is generated in the biotransformation process. Moreover, celastrol-29-O-β-glucoside may serve as a potential candidate in the future medicine application due to its higher water solubility and lower toxicity.

Original languageEnglish
Pages (from-to)176-182
Number of pages7
JournalJournal of Bioscience and Bioengineering
Volume131
Issue number2
DOIs
Publication statusPublished - Feb 2021

Keywords

  • Bacillus
  • Biotransformation
  • Celastrol
  • Glycosyltransferase
  • Triterpenoid

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

Fingerprint

Dive into the research topics of 'Biotransformation of celastrol to a novel, well-soluble, low-toxic and anti-oxidative celastrol-29-O-β-glucoside by Bacillus glycosyltransferases'. Together they form a unique fingerprint.

Cite this