Friedelane-type triterpene cyclase in celastrol biosynthesis from Tripterygium wilfordii and its application for triterpenes biosynthesis in yeast

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.

Bibliographische Detailangaben
Veröffentlicht in:The New phytologist. - 1979. - 223(2019), 2 vom: 01. Juli, Seite 722-735
1. Verfasser: Zhou, Jiawei (VerfasserIn)
Weitere Verfasser: Hu, Tianyuan, Gao, Linhui, Su, Ping, Zhang, Yifeng, Zhao, Yujun, Chen, Shang, Tu, Lichan, Song, Yadi, Wang, Xing, Huang, Luqi, Gao, Wei
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2019
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... Pentacyclic Triterpenes RNA, Messenger Triterpenes friedelane methyl jasmonate 900N171A0F Intramolecular Transferases EC 5.4.- L8GG98663L
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100 1 |a Zhou, Jiawei  |e verfasserin  |4 aut 
245 1 0 |a Friedelane-type triterpene cyclase in celastrol biosynthesis from Tripterygium wilfordii and its application for triterpenes biosynthesis in yeast 
264 1 |c 2019 
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500 |a Date Completed 02.03.2020 
500 |a Date Revised 04.12.2021 
500 |a published: Print-Electronic 
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500 |a Citation Status MEDLINE 
520 |a © 2019 The Authors. New Phytologist © 2019 New Phytologist Trust. 
520 |a 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 
650 4 |a Journal Article 
650 4 |a Research Support, Non-U.S. Gov't 
650 4 |a Tripterygium wilfordii 
650 4 |a biosynthesis 
650 4 |a celastrol 
650 4 |a oxidosqualene cyclases (OSC) 
650 4 |a triterpenes 
650 7 |a Acetates  |2 NLM 
650 7 |a Cyclopentanes  |2 NLM 
650 7 |a Oxylipins  |2 NLM 
650 7 |a Pentacyclic Triterpenes  |2 NLM 
650 7 |a RNA, Messenger  |2 NLM 
650 7 |a Triterpenes  |2 NLM 
650 7 |a friedelane  |2 NLM 
650 7 |a methyl jasmonate  |2 NLM 
650 7 |a 900N171A0F  |2 NLM 
650 7 |a Intramolecular Transferases  |2 NLM 
650 7 |a EC 5.4.-  |2 NLM 
650 7 |a celastrol  |2 NLM 
650 7 |a L8GG98663L  |2 NLM 
700 1 |a Hu, Tianyuan  |e verfasserin  |4 aut 
700 1 |a Gao, Linhui  |e verfasserin  |4 aut 
700 1 |a Su, Ping  |e verfasserin  |4 aut 
700 1 |a Zhang, Yifeng  |e verfasserin  |4 aut 
700 1 |a Zhao, Yujun  |e verfasserin  |4 aut 
700 1 |a Chen, Shang  |e verfasserin  |4 aut 
700 1 |a Tu, Lichan  |e verfasserin  |4 aut 
700 1 |a Song, Yadi  |e verfasserin  |4 aut 
700 1 |a Wang, Xing  |e verfasserin  |4 aut 
700 1 |a Huang, Luqi  |e verfasserin  |4 aut 
700 1 |a Gao, Wei  |e verfasserin  |4 aut 
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773 1 8 |g volume:223  |g year:2019  |g number:2  |g day:01  |g month:07  |g pages:722-735 
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