The Biosynthesis and Transport of Ophiobolins in <i>Aspergillus ustus</i> 094102
Ophiobolins are a group of sesterterpenoids with a 5-8-5 tricyclic skeleton. They exhibit a significant cytotoxicity and present potential medicinal prospects. However, the biosynthesis and transport mechanisms of these valuable compounds have not been fully resolved. Herein, based on a transcriptom...
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MDPI AG
2022-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/3/1903 |
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| author | Jingjing Yan Jiamin Pang Jianjia Liang Wulin Yu Xuequn Liao Ayikaimaier Aobulikasimu Xinrui Yi Yapeng Yin Zixin Deng Kui Hong |
| author_facet | Jingjing Yan Jiamin Pang Jianjia Liang Wulin Yu Xuequn Liao Ayikaimaier Aobulikasimu Xinrui Yi Yapeng Yin Zixin Deng Kui Hong |
| author_sort | Jingjing Yan |
| collection | DOAJ |
| description | Ophiobolins are a group of sesterterpenoids with a 5-8-5 tricyclic skeleton. They exhibit a significant cytotoxicity and present potential medicinal prospects. However, the biosynthesis and transport mechanisms of these valuable compounds have not been fully resolved. Herein, based on a transcriptome analysis, gene inactivation, heterologous expression and feeding experiments, we fully explain the biosynthesis pathway of ophiobolin K in <i>Aspergillus ustus</i> 094102, especially proved to be an unclustered oxidase OblC<sub>Au</sub> that catalyzes dehydrogenation at the site of C16 and C17 of both ophiobolin F and ophiobolin C. We also find that the intermediate ophiobolin C and final product ophiobolin K could be transported into a space between the cell wall and membrane by OblD<sub>Au</sub> to avoid the inhibiting of cell growth, which is proved by a fluorescence observation of the subcellular localization and cytotoxicity tests. This study completely resolves the biosynthesis mechanism of ophiobolins in strain <i>A</i><i>. ustus</i> 094102. At the same time, it is revealed that the burden of strain growth caused by the excessive accumulation and toxicity of secondary metabolites is closely related to compartmentalized biosynthesis. |
| first_indexed | 2024-03-09T23:43:19Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T23:43:19Z |
| publishDate | 2022-02-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e35126d8c53843bbb70d8758db69be4d2023-11-23T16:48:32ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-02-01233190310.3390/ijms23031903The Biosynthesis and Transport of Ophiobolins in <i>Aspergillus ustus</i> 094102Jingjing Yan0Jiamin Pang1Jianjia Liang2Wulin Yu3Xuequn Liao4Ayikaimaier Aobulikasimu5Xinrui Yi6Yapeng Yin7Zixin Deng8Kui Hong9Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, ChinaKey Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, ChinaKey Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, ChinaKey Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, ChinaKey Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, ChinaKey Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, ChinaKey Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, ChinaKey Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, ChinaKey Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, ChinaKey Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, ChinaOphiobolins are a group of sesterterpenoids with a 5-8-5 tricyclic skeleton. They exhibit a significant cytotoxicity and present potential medicinal prospects. However, the biosynthesis and transport mechanisms of these valuable compounds have not been fully resolved. Herein, based on a transcriptome analysis, gene inactivation, heterologous expression and feeding experiments, we fully explain the biosynthesis pathway of ophiobolin K in <i>Aspergillus ustus</i> 094102, especially proved to be an unclustered oxidase OblC<sub>Au</sub> that catalyzes dehydrogenation at the site of C16 and C17 of both ophiobolin F and ophiobolin C. We also find that the intermediate ophiobolin C and final product ophiobolin K could be transported into a space between the cell wall and membrane by OblD<sub>Au</sub> to avoid the inhibiting of cell growth, which is proved by a fluorescence observation of the subcellular localization and cytotoxicity tests. This study completely resolves the biosynthesis mechanism of ophiobolins in strain <i>A</i><i>. ustus</i> 094102. At the same time, it is revealed that the burden of strain growth caused by the excessive accumulation and toxicity of secondary metabolites is closely related to compartmentalized biosynthesis.https://www.mdpi.com/1422-0067/23/3/1903ophiobolinsunclustered oxidasetransportercompartmentalized biosynthesis |
| spellingShingle | Jingjing Yan Jiamin Pang Jianjia Liang Wulin Yu Xuequn Liao Ayikaimaier Aobulikasimu Xinrui Yi Yapeng Yin Zixin Deng Kui Hong The Biosynthesis and Transport of Ophiobolins in <i>Aspergillus ustus</i> 094102 International Journal of Molecular Sciences ophiobolins unclustered oxidase transporter compartmentalized biosynthesis |
| title | The Biosynthesis and Transport of Ophiobolins in <i>Aspergillus ustus</i> 094102 |
| title_full | The Biosynthesis and Transport of Ophiobolins in <i>Aspergillus ustus</i> 094102 |
| title_fullStr | The Biosynthesis and Transport of Ophiobolins in <i>Aspergillus ustus</i> 094102 |
| title_full_unstemmed | The Biosynthesis and Transport of Ophiobolins in <i>Aspergillus ustus</i> 094102 |
| title_short | The Biosynthesis and Transport of Ophiobolins in <i>Aspergillus ustus</i> 094102 |
| title_sort | biosynthesis and transport of ophiobolins in i aspergillus ustus i 094102 |
| topic | ophiobolins unclustered oxidase transporter compartmentalized biosynthesis |
| url | https://www.mdpi.com/1422-0067/23/3/1903 |
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