Systems Metabolic Engineering of <i<Saccharomyces cerevisiae</i< for the High-Level Production of (2<i<S</i<)-Eriodictyol
(2<i<S</i<)-eriodictyol (ERD) is a flavonoid widely found in citrus fruits, vegetables, and important medicinal plants with neuroprotective, cardioprotective, antidiabetic, and anti-obesity effects. However, the microbial synthesis of ERD is limited by complex metabolic pathways and ofte...
Ausführliche Beschreibung
Autor*in: |
Siqi Zhang [verfasserIn] Juan Liu [verfasserIn] Zhiqiang Xiao [verfasserIn] Xinjia Tan [verfasserIn] Yongtong Wang [verfasserIn] Yifei Zhao [verfasserIn] Ning Jiang [verfasserIn] Yang Shan [verfasserIn] |
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Format: |
E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2024 |
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Übergeordnetes Werk: |
In: Journal of Fungi - MDPI AG, 2015, 10(2024), 2, p 119 |
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Übergeordnetes Werk: |
volume:10 ; year:2024 ; number:2, p 119 |
Links: |
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DOI / URN: |
10.3390/jof10020119 |
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Katalog-ID: |
DOAJ099622912 |
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520 | |a (2<i<S</i<)-eriodictyol (ERD) is a flavonoid widely found in citrus fruits, vegetables, and important medicinal plants with neuroprotective, cardioprotective, antidiabetic, and anti-obesity effects. However, the microbial synthesis of ERD is limited by complex metabolic pathways and often results in a low production performance. Here, we engineered <i<Saccharomyces cerevisiae</i< by fine-tuning the metabolism of the ERD synthesis pathway. The results showed that the ERD titer was effectively increased, and the intermediate metabolites levels were reduced. First, we successfully reconstructed the de novo synthesis pathway of <i<p</i<-coumaric acid in <i<S. cerevisiae</i< and fine-tuned the metabolic pathway using promoter engineering and terminator engineering for the high-level production of (2<i<S</i<)-naringenin. Subsequently, the synthesis of ERD was achieved by introducing the <i<ThF3</i<′<i<H</i< gene from <i<Tricyrtis hirta</i<. Finally, by multiplying the copy number of the <i<ThF3</i<′<i<H</i< gene, the production of ERD was further increased, reaching 132.08 mg L<sup<−1</sup<. Our work emphasizes the importance of regulating the metabolic balance to produce natural products in microbial cell factories. | ||
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10.3390/jof10020119 doi (DE-627)DOAJ099622912 (DE-599)DOAJa5f53691a43f49c59c1b1975f7c02b54 DE-627 ger DE-627 rakwb eng QH301-705.5 Siqi Zhang verfasserin aut Systems Metabolic Engineering of <i<Saccharomyces cerevisiae</i< for the High-Level Production of (2<i<S</i<)-Eriodictyol 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier (2<i<S</i<)-eriodictyol (ERD) is a flavonoid widely found in citrus fruits, vegetables, and important medicinal plants with neuroprotective, cardioprotective, antidiabetic, and anti-obesity effects. However, the microbial synthesis of ERD is limited by complex metabolic pathways and often results in a low production performance. Here, we engineered <i<Saccharomyces cerevisiae</i< by fine-tuning the metabolism of the ERD synthesis pathway. The results showed that the ERD titer was effectively increased, and the intermediate metabolites levels were reduced. First, we successfully reconstructed the de novo synthesis pathway of <i<p</i<-coumaric acid in <i<S. cerevisiae</i< and fine-tuned the metabolic pathway using promoter engineering and terminator engineering for the high-level production of (2<i<S</i<)-naringenin. Subsequently, the synthesis of ERD was achieved by introducing the <i<ThF3</i<′<i<H</i< gene from <i<Tricyrtis hirta</i<. Finally, by multiplying the copy number of the <i<ThF3</i<′<i<H</i< gene, the production of ERD was further increased, reaching 132.08 mg L<sup<−1</sup<. Our work emphasizes the importance of regulating the metabolic balance to produce natural products in microbial cell factories. flavonoid (2<i<S</i<)-naringenin (2<i<S</i<)-eriodictyol metabolic engineering metabolic balance Biology (General) Juan Liu verfasserin aut Zhiqiang Xiao verfasserin aut Xinjia Tan verfasserin aut Yongtong Wang verfasserin aut Yifei Zhao verfasserin aut Ning Jiang verfasserin aut Yang Shan verfasserin aut In Journal of Fungi MDPI AG, 2015 10(2024), 2, p 119 (DE-627)796588538 (DE-600)2784229-0 2309608X nnns volume:10 year:2024 number:2, p 119 https://doi.org/10.3390/jof10020119 kostenfrei https://doaj.org/article/a5f53691a43f49c59c1b1975f7c02b54 kostenfrei https://www.mdpi.com/2309-608X/10/2/119 kostenfrei https://doaj.org/toc/2309-608X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2024 2, p 119 |
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10.3390/jof10020119 doi (DE-627)DOAJ099622912 (DE-599)DOAJa5f53691a43f49c59c1b1975f7c02b54 DE-627 ger DE-627 rakwb eng QH301-705.5 Siqi Zhang verfasserin aut Systems Metabolic Engineering of <i<Saccharomyces cerevisiae</i< for the High-Level Production of (2<i<S</i<)-Eriodictyol 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier (2<i<S</i<)-eriodictyol (ERD) is a flavonoid widely found in citrus fruits, vegetables, and important medicinal plants with neuroprotective, cardioprotective, antidiabetic, and anti-obesity effects. However, the microbial synthesis of ERD is limited by complex metabolic pathways and often results in a low production performance. Here, we engineered <i<Saccharomyces cerevisiae</i< by fine-tuning the metabolism of the ERD synthesis pathway. The results showed that the ERD titer was effectively increased, and the intermediate metabolites levels were reduced. First, we successfully reconstructed the de novo synthesis pathway of <i<p</i<-coumaric acid in <i<S. cerevisiae</i< and fine-tuned the metabolic pathway using promoter engineering and terminator engineering for the high-level production of (2<i<S</i<)-naringenin. Subsequently, the synthesis of ERD was achieved by introducing the <i<ThF3</i<′<i<H</i< gene from <i<Tricyrtis hirta</i<. Finally, by multiplying the copy number of the <i<ThF3</i<′<i<H</i< gene, the production of ERD was further increased, reaching 132.08 mg L<sup<−1</sup<. Our work emphasizes the importance of regulating the metabolic balance to produce natural products in microbial cell factories. flavonoid (2<i<S</i<)-naringenin (2<i<S</i<)-eriodictyol metabolic engineering metabolic balance Biology (General) Juan Liu verfasserin aut Zhiqiang Xiao verfasserin aut Xinjia Tan verfasserin aut Yongtong Wang verfasserin aut Yifei Zhao verfasserin aut Ning Jiang verfasserin aut Yang Shan verfasserin aut In Journal of Fungi MDPI AG, 2015 10(2024), 2, p 119 (DE-627)796588538 (DE-600)2784229-0 2309608X nnns volume:10 year:2024 number:2, p 119 https://doi.org/10.3390/jof10020119 kostenfrei https://doaj.org/article/a5f53691a43f49c59c1b1975f7c02b54 kostenfrei https://www.mdpi.com/2309-608X/10/2/119 kostenfrei https://doaj.org/toc/2309-608X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2024 2, p 119 |
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10.3390/jof10020119 doi (DE-627)DOAJ099622912 (DE-599)DOAJa5f53691a43f49c59c1b1975f7c02b54 DE-627 ger DE-627 rakwb eng QH301-705.5 Siqi Zhang verfasserin aut Systems Metabolic Engineering of <i<Saccharomyces cerevisiae</i< for the High-Level Production of (2<i<S</i<)-Eriodictyol 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier (2<i<S</i<)-eriodictyol (ERD) is a flavonoid widely found in citrus fruits, vegetables, and important medicinal plants with neuroprotective, cardioprotective, antidiabetic, and anti-obesity effects. However, the microbial synthesis of ERD is limited by complex metabolic pathways and often results in a low production performance. Here, we engineered <i<Saccharomyces cerevisiae</i< by fine-tuning the metabolism of the ERD synthesis pathway. The results showed that the ERD titer was effectively increased, and the intermediate metabolites levels were reduced. First, we successfully reconstructed the de novo synthesis pathway of <i<p</i<-coumaric acid in <i<S. cerevisiae</i< and fine-tuned the metabolic pathway using promoter engineering and terminator engineering for the high-level production of (2<i<S</i<)-naringenin. Subsequently, the synthesis of ERD was achieved by introducing the <i<ThF3</i<′<i<H</i< gene from <i<Tricyrtis hirta</i<. Finally, by multiplying the copy number of the <i<ThF3</i<′<i<H</i< gene, the production of ERD was further increased, reaching 132.08 mg L<sup<−1</sup<. Our work emphasizes the importance of regulating the metabolic balance to produce natural products in microbial cell factories. flavonoid (2<i<S</i<)-naringenin (2<i<S</i<)-eriodictyol metabolic engineering metabolic balance Biology (General) Juan Liu verfasserin aut Zhiqiang Xiao verfasserin aut Xinjia Tan verfasserin aut Yongtong Wang verfasserin aut Yifei Zhao verfasserin aut Ning Jiang verfasserin aut Yang Shan verfasserin aut In Journal of Fungi MDPI AG, 2015 10(2024), 2, p 119 (DE-627)796588538 (DE-600)2784229-0 2309608X nnns volume:10 year:2024 number:2, p 119 https://doi.org/10.3390/jof10020119 kostenfrei https://doaj.org/article/a5f53691a43f49c59c1b1975f7c02b54 kostenfrei https://www.mdpi.com/2309-608X/10/2/119 kostenfrei https://doaj.org/toc/2309-608X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2024 2, p 119 |
allfieldsGer |
10.3390/jof10020119 doi (DE-627)DOAJ099622912 (DE-599)DOAJa5f53691a43f49c59c1b1975f7c02b54 DE-627 ger DE-627 rakwb eng QH301-705.5 Siqi Zhang verfasserin aut Systems Metabolic Engineering of <i<Saccharomyces cerevisiae</i< for the High-Level Production of (2<i<S</i<)-Eriodictyol 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier (2<i<S</i<)-eriodictyol (ERD) is a flavonoid widely found in citrus fruits, vegetables, and important medicinal plants with neuroprotective, cardioprotective, antidiabetic, and anti-obesity effects. However, the microbial synthesis of ERD is limited by complex metabolic pathways and often results in a low production performance. Here, we engineered <i<Saccharomyces cerevisiae</i< by fine-tuning the metabolism of the ERD synthesis pathway. The results showed that the ERD titer was effectively increased, and the intermediate metabolites levels were reduced. First, we successfully reconstructed the de novo synthesis pathway of <i<p</i<-coumaric acid in <i<S. cerevisiae</i< and fine-tuned the metabolic pathway using promoter engineering and terminator engineering for the high-level production of (2<i<S</i<)-naringenin. Subsequently, the synthesis of ERD was achieved by introducing the <i<ThF3</i<′<i<H</i< gene from <i<Tricyrtis hirta</i<. Finally, by multiplying the copy number of the <i<ThF3</i<′<i<H</i< gene, the production of ERD was further increased, reaching 132.08 mg L<sup<−1</sup<. Our work emphasizes the importance of regulating the metabolic balance to produce natural products in microbial cell factories. flavonoid (2<i<S</i<)-naringenin (2<i<S</i<)-eriodictyol metabolic engineering metabolic balance Biology (General) Juan Liu verfasserin aut Zhiqiang Xiao verfasserin aut Xinjia Tan verfasserin aut Yongtong Wang verfasserin aut Yifei Zhao verfasserin aut Ning Jiang verfasserin aut Yang Shan verfasserin aut In Journal of Fungi MDPI AG, 2015 10(2024), 2, p 119 (DE-627)796588538 (DE-600)2784229-0 2309608X nnns volume:10 year:2024 number:2, p 119 https://doi.org/10.3390/jof10020119 kostenfrei https://doaj.org/article/a5f53691a43f49c59c1b1975f7c02b54 kostenfrei https://www.mdpi.com/2309-608X/10/2/119 kostenfrei https://doaj.org/toc/2309-608X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2024 2, p 119 |
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10.3390/jof10020119 doi (DE-627)DOAJ099622912 (DE-599)DOAJa5f53691a43f49c59c1b1975f7c02b54 DE-627 ger DE-627 rakwb eng QH301-705.5 Siqi Zhang verfasserin aut Systems Metabolic Engineering of <i<Saccharomyces cerevisiae</i< for the High-Level Production of (2<i<S</i<)-Eriodictyol 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier (2<i<S</i<)-eriodictyol (ERD) is a flavonoid widely found in citrus fruits, vegetables, and important medicinal plants with neuroprotective, cardioprotective, antidiabetic, and anti-obesity effects. However, the microbial synthesis of ERD is limited by complex metabolic pathways and often results in a low production performance. Here, we engineered <i<Saccharomyces cerevisiae</i< by fine-tuning the metabolism of the ERD synthesis pathway. The results showed that the ERD titer was effectively increased, and the intermediate metabolites levels were reduced. First, we successfully reconstructed the de novo synthesis pathway of <i<p</i<-coumaric acid in <i<S. cerevisiae</i< and fine-tuned the metabolic pathway using promoter engineering and terminator engineering for the high-level production of (2<i<S</i<)-naringenin. Subsequently, the synthesis of ERD was achieved by introducing the <i<ThF3</i<′<i<H</i< gene from <i<Tricyrtis hirta</i<. Finally, by multiplying the copy number of the <i<ThF3</i<′<i<H</i< gene, the production of ERD was further increased, reaching 132.08 mg L<sup<−1</sup<. Our work emphasizes the importance of regulating the metabolic balance to produce natural products in microbial cell factories. flavonoid (2<i<S</i<)-naringenin (2<i<S</i<)-eriodictyol metabolic engineering metabolic balance Biology (General) Juan Liu verfasserin aut Zhiqiang Xiao verfasserin aut Xinjia Tan verfasserin aut Yongtong Wang verfasserin aut Yifei Zhao verfasserin aut Ning Jiang verfasserin aut Yang Shan verfasserin aut In Journal of Fungi MDPI AG, 2015 10(2024), 2, p 119 (DE-627)796588538 (DE-600)2784229-0 2309608X nnns volume:10 year:2024 number:2, p 119 https://doi.org/10.3390/jof10020119 kostenfrei https://doaj.org/article/a5f53691a43f49c59c1b1975f7c02b54 kostenfrei https://www.mdpi.com/2309-608X/10/2/119 kostenfrei https://doaj.org/toc/2309-608X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2024 2, p 119 |
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QH301-705.5 Systems Metabolic Engineering of <i<Saccharomyces cerevisiae</i< for the High-Level Production of (2<i<S</i<)-Eriodictyol flavonoid (2<i<S</i<)-naringenin (2<i<S</i<)-eriodictyol metabolic engineering metabolic balance |
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Systems Metabolic Engineering of <i<Saccharomyces cerevisiae</i< for the High-Level Production of (2<i<S</i<)-Eriodictyol |
abstract |
(2<i<S</i<)-eriodictyol (ERD) is a flavonoid widely found in citrus fruits, vegetables, and important medicinal plants with neuroprotective, cardioprotective, antidiabetic, and anti-obesity effects. However, the microbial synthesis of ERD is limited by complex metabolic pathways and often results in a low production performance. Here, we engineered <i<Saccharomyces cerevisiae</i< by fine-tuning the metabolism of the ERD synthesis pathway. The results showed that the ERD titer was effectively increased, and the intermediate metabolites levels were reduced. First, we successfully reconstructed the de novo synthesis pathway of <i<p</i<-coumaric acid in <i<S. cerevisiae</i< and fine-tuned the metabolic pathway using promoter engineering and terminator engineering for the high-level production of (2<i<S</i<)-naringenin. Subsequently, the synthesis of ERD was achieved by introducing the <i<ThF3</i<′<i<H</i< gene from <i<Tricyrtis hirta</i<. Finally, by multiplying the copy number of the <i<ThF3</i<′<i<H</i< gene, the production of ERD was further increased, reaching 132.08 mg L<sup<−1</sup<. Our work emphasizes the importance of regulating the metabolic balance to produce natural products in microbial cell factories. |
abstractGer |
(2<i<S</i<)-eriodictyol (ERD) is a flavonoid widely found in citrus fruits, vegetables, and important medicinal plants with neuroprotective, cardioprotective, antidiabetic, and anti-obesity effects. However, the microbial synthesis of ERD is limited by complex metabolic pathways and often results in a low production performance. Here, we engineered <i<Saccharomyces cerevisiae</i< by fine-tuning the metabolism of the ERD synthesis pathway. The results showed that the ERD titer was effectively increased, and the intermediate metabolites levels were reduced. First, we successfully reconstructed the de novo synthesis pathway of <i<p</i<-coumaric acid in <i<S. cerevisiae</i< and fine-tuned the metabolic pathway using promoter engineering and terminator engineering for the high-level production of (2<i<S</i<)-naringenin. Subsequently, the synthesis of ERD was achieved by introducing the <i<ThF3</i<′<i<H</i< gene from <i<Tricyrtis hirta</i<. Finally, by multiplying the copy number of the <i<ThF3</i<′<i<H</i< gene, the production of ERD was further increased, reaching 132.08 mg L<sup<−1</sup<. Our work emphasizes the importance of regulating the metabolic balance to produce natural products in microbial cell factories. |
abstract_unstemmed |
(2<i<S</i<)-eriodictyol (ERD) is a flavonoid widely found in citrus fruits, vegetables, and important medicinal plants with neuroprotective, cardioprotective, antidiabetic, and anti-obesity effects. However, the microbial synthesis of ERD is limited by complex metabolic pathways and often results in a low production performance. Here, we engineered <i<Saccharomyces cerevisiae</i< by fine-tuning the metabolism of the ERD synthesis pathway. The results showed that the ERD titer was effectively increased, and the intermediate metabolites levels were reduced. First, we successfully reconstructed the de novo synthesis pathway of <i<p</i<-coumaric acid in <i<S. cerevisiae</i< and fine-tuned the metabolic pathway using promoter engineering and terminator engineering for the high-level production of (2<i<S</i<)-naringenin. Subsequently, the synthesis of ERD was achieved by introducing the <i<ThF3</i<′<i<H</i< gene from <i<Tricyrtis hirta</i<. Finally, by multiplying the copy number of the <i<ThF3</i<′<i<H</i< gene, the production of ERD was further increased, reaching 132.08 mg L<sup<−1</sup<. Our work emphasizes the importance of regulating the metabolic balance to produce natural products in microbial cell factories. |
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However, the microbial synthesis of ERD is limited by complex metabolic pathways and often results in a low production performance. Here, we engineered <i<Saccharomyces cerevisiae</i< by fine-tuning the metabolism of the ERD synthesis pathway. The results showed that the ERD titer was effectively increased, and the intermediate metabolites levels were reduced. First, we successfully reconstructed the de novo synthesis pathway of <i<p</i<-coumaric acid in <i<S. cerevisiae</i< and fine-tuned the metabolic pathway using promoter engineering and terminator engineering for the high-level production of (2<i<S</i<)-naringenin. Subsequently, the synthesis of ERD was achieved by introducing the <i<ThF3</i<′<i<H</i< gene from <i<Tricyrtis hirta</i<. Finally, by multiplying the copy number of the <i<ThF3</i<′<i<H</i< gene, the production of ERD was further increased, reaching 132.08 mg L<sup<−1</sup<. 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