Cryptic piperazine derivatives activated by knocking out the global regulator LaeA in Aspergillus flavipes
Copyright © 2024 Elsevier Ltd. All rights reserved..
Genome sequencing on an intertidal zone-derived Aspergillus flavipes strain revealed its great potential to produce secondary metabolites. To activate the cryptic compounds of A. flavipes, the global regulator flLaeA was knocked out, leading to substantial up-regulation of the expression of two NRPS-like biosynthetic gene clusters in the ΔflLaeA mutant. With a scaled-up fermentation of the ΔflLaeA strain, five compounds, including two previously undescribed piperazine derivatives flavipamides A and B (1 and 2), along with three known compounds (3-5), were obtained by LC-MS guided isolation. The new compounds were elucidated by spectroscopic analysis and electronic circular dichroism (ECD) calculations, and the biosynthetic pathway was proposed on the bias of bioinformatic analysis and 13C isotope labeling evidence. This is the first report to access cryptic fungi secondary metabolites by inactivating global regulator LaeA and may provide a new approach to discovering new secondary metabolites by such genetic manipulation.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:103 |
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| Enthalten in: |
Bioorganic & medicinal chemistry - 103(2024) vom: 01. Apr., Seite 117685 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Liu, Yaping [VerfasserIn] |
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| Links: |
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| Themen: |
Aspergillus flavipes |
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| Anmerkungen: |
Date Completed 05.04.2024 Date Revised 05.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bmc.2024.117685 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Genome sequencing on an intertidal zone-derived Aspergillus flavipes strain revealed its great potential to produce secondary metabolites. To activate the cryptic compounds of A. flavipes, the global regulator flLaeA was knocked out, leading to substantial up-regulation of the expression of two NRPS-like biosynthetic gene clusters in the ΔflLaeA mutant. With a scaled-up fermentation of the ΔflLaeA strain, five compounds, including two previously undescribed piperazine derivatives flavipamides A and B (1 and 2), along with three known compounds (3-5), were obtained by LC-MS guided isolation. The new compounds were elucidated by spectroscopic analysis and electronic circular dichroism (ECD) calculations, and the biosynthetic pathway was proposed on the bias of bioinformatic analysis and 13C isotope labeling evidence. This is the first report to access cryptic fungi secondary metabolites by inactivating global regulator LaeA and may provide a new approach to discovering new secondary metabolites by such genetic manipulation | ||
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| 700 | 1 | |a Li, Pengkun |e verfasserin |4 aut | |
| 700 | 1 | |a Qi, Changxing |e verfasserin |4 aut | |
| 700 | 1 | |a Zha, Ziou |e verfasserin |4 aut | |
| 700 | 1 | |a Meng, Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Chang |e verfasserin |4 aut | |
| 700 | 1 | |a Han, Jiapei |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Qun |e verfasserin |4 aut | |
| 700 | 1 | |a Luo, Zengwei |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jianping |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Hucheng |e verfasserin |4 aut | |
| 700 | 1 | |a Ye, Ying |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Chunmei |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Yuan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yonghui |e verfasserin |4 aut | |
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