Friedelane-type triterpene cyclase in celastrol biosynthesis from Tripterygium wilfordii and its application for triterpenes biosynthesis in yeast
© 2019 The Authors. New Phytologist © 2019 New Phytologist Trust.
| Veröffentlicht in: | The New phytologist. - 1979. - 223(2019), 2 vom: 01. Juli, Seite 722-735 |
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| Weitere Verfasser: | , , , , , , , , , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2019
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| Zugriff auf das übergeordnete Werk: | The New phytologist |
| Schlagworte: | Journal Article Research Support, Non-U.S. Gov't Tripterygium wilfordii biosynthesis celastrol oxidosqualene cyclases (OSC) triterpenes Acetates Cyclopentanes Oxylipins mehr... |
| Zusammenfassung: | © 2019 The Authors. New Phytologist © 2019 New Phytologist Trust. Celastrol is a promising bioactive compound isolated from Tripterygium wilfordii and has been shown to possess many encouraging preclinical applications. However, the celastrol biosynthetic pathway is poorly understood, especially the key oxidosqualene cyclase (OSC) enzyme responsible for cyclisation of the main scaffold. Here, we report on the isolation and characterisation of three OSCs from T. wilfordii: TwOSC1, TwOSC2 and TwOSC3. Both TwOSC1 and TwOSC3 were multiproduct friedelin synthases, while TwOSC2 was a β-amyrin synthase. We further found that TwOSC1 and TwOSC3 were involved in the biosynthesis of celastrol and that their common product, friedelin, was a precursor of celastrol. We then reconstituted the biosynthetic pathway of friedelin in engineered yeast constructed by the CRISPR/Cas9 system, with protein modification and medium optimisation, leading to heterologous production of friedelin at 37.07 mg l-1 in a shake flask culture. Our study was the first to identify the genes responsible for biosynthesis of the main scaffold of celastrol and other triterpenes in T. wilfordii. As friedelin has been found in many plants, the results and approaches described here have laid a solid foundation for further explaining the biosynthesis of celastrol and related triterpenoids. Moreover, our results provide insights for metabolic engineering of friedelane-type triterpenes |
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| Beschreibung: | Date Completed 02.03.2020 Date Revised 04.12.2021 published: Print-Electronic GENBANK: SRR6001265, KY885467, KY885468, KY885469 Citation Status MEDLINE |
| ISSN: | 1469-8137 |
| DOI: | 10.1111/nph.15809 |