Efficient De Novo Biosynthesis of Curcumin in Escherichia coli by Optimizing Pathway Modules and Increasing the Malonyl-CoA Supply
Curcumin is a natural phenylpropanoid compound with various biological activities and is widely used in food and pharmaceuticals. A de novo curcumin biosynthetic pathway was constructed in Escherichia coli BL21(DE3). Optimization of the curcumin biosynthesis module achieved a curcumin titer of 26.8 ± 0.6 mg/L. Regulating the metabolic fluxes of the β-oxidation pathway and fatty acid elongation cycle and blocking the endogenous malonyl-CoA consumption pathway increased the titer to 113.6 ± 7.1 mg/L. Knockout of endogenous curcumin reductase (curA) and intermediate product detoxification by heterologous expression of the solvent-resistant pump (srpB) increased the titer to 137.5 ± 3.0 mg/L. A 5 L pilot-scale fermentation, using a three-stage pH alternation strategy, increased the titer to 696.2 ± 20.9 mg/L, 178.5-fold higher than the highest curcumin titer from de novo biosynthesis previously reported, thereby laying the foundation for efficient biosynthesis of curcumin and its derivatives.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2024 |
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Erschienen: |
2024 |
Enthalten in: |
Zur Gesamtaufnahme - volume:72 |
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Enthalten in: |
Journal of agricultural and food chemistry - 72(2024), 1 vom: 10. Jan., Seite 566-576 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Chen, Jianbin [VerfasserIn] |
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Links: |
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Themen: |
524-14-1 |
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Anmerkungen: |
Date Completed 11.01.2024 Date Revised 11.01.2024 published: Print-Electronic Citation Status MEDLINE |
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doi: |
10.1021/acs.jafc.3c07379 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM366447300 |
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520 | |a Curcumin is a natural phenylpropanoid compound with various biological activities and is widely used in food and pharmaceuticals. A de novo curcumin biosynthetic pathway was constructed in Escherichia coli BL21(DE3). Optimization of the curcumin biosynthesis module achieved a curcumin titer of 26.8 ± 0.6 mg/L. Regulating the metabolic fluxes of the β-oxidation pathway and fatty acid elongation cycle and blocking the endogenous malonyl-CoA consumption pathway increased the titer to 113.6 ± 7.1 mg/L. Knockout of endogenous curcumin reductase (curA) and intermediate product detoxification by heterologous expression of the solvent-resistant pump (srpB) increased the titer to 137.5 ± 3.0 mg/L. A 5 L pilot-scale fermentation, using a three-stage pH alternation strategy, increased the titer to 696.2 ± 20.9 mg/L, 178.5-fold higher than the highest curcumin titer from de novo biosynthesis previously reported, thereby laying the foundation for efficient biosynthesis of curcumin and its derivatives | ||
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700 | 1 | |a Wang, Huijing |e verfasserin |4 aut | |
700 | 1 | |a Hu, MingLong |e verfasserin |4 aut | |
700 | 1 | |a Zhou, Jingwen |e verfasserin |4 aut | |
700 | 1 | |a Du, Guocheng |e verfasserin |4 aut | |
700 | 1 | |a Zeng, Weizhu |e verfasserin |4 aut | |
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