Metabolic engineering strategies for naringenin production enhancement in Streptomyces albidoflavus J1074
Abstract Background Naringenin is an industrially relevant compound due to its multiple pharmaceutical properties as well as its central role in flavonoid biosynthesis. Results On our way to develop Streptomyces albidoflavus J1074 as a microbial cell factory for naringenin production, we have signif...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-08-01
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| Series: | Microbial Cell Factories |
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| Online Access: | https://doi.org/10.1186/s12934-023-02172-5 |
| _version_ | 1797450978469871616 |
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| author | Suhui Ye Patricia Magadán-Corpas Álvaro Pérez-Valero Claudio J. Villar Felipe Lombó |
| author_facet | Suhui Ye Patricia Magadán-Corpas Álvaro Pérez-Valero Claudio J. Villar Felipe Lombó |
| author_sort | Suhui Ye |
| collection | DOAJ |
| description | Abstract Background Naringenin is an industrially relevant compound due to its multiple pharmaceutical properties as well as its central role in flavonoid biosynthesis. Results On our way to develop Streptomyces albidoflavus J1074 as a microbial cell factory for naringenin production, we have significantly increased the yields of this flavanone by combining various metabolic engineering strategies, fermentation strategies and genome editing approaches in a stepwise manner. Specifically, we have screened different cultivation media to identify the optimal production conditions and have investigated how the additive feeding of naringenin precursors influences the production. Furthermore, we have employed genome editing strategies to remove biosynthetic gene clusters (BGCs) associated with pathways that might compete with naringenin biosynthesis for malonyl-CoA precursors. Moreover, we have expressed MatBC, coding for a malonate transporter and an enzyme responsible for the conversion of malonate into malonyl-CoA, respectively, and have duplicated the naringenin BGC, further contributing to the production improvement. By combining all of these strategies, we were able to achieve a remarkable 375-fold increase (from 0.06 mg/L to 22.47 mg/L) in naringenin titers. Conclusion This work demonstrates the influence that fermentation conditions have over the final yield of a bioactive compound of interest and highlights various bottlenecks that affect production. Once such bottlenecks are identified, different strategies can be applied to overcome them, although the efficiencies of such strategies may vary and are difficult to predict. |
| first_indexed | 2024-03-09T14:48:18Z |
| format | Article |
| id | doaj.art-6551db8552f048a08ad2e3d59ccb978f |
| institution | Directory Open Access Journal |
| issn | 1475-2859 |
| language | English |
| last_indexed | 2024-03-09T14:48:18Z |
| publishDate | 2023-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Microbial Cell Factories |
| spelling | doaj.art-6551db8552f048a08ad2e3d59ccb978f2023-11-26T14:37:58ZengBMCMicrobial Cell Factories1475-28592023-08-0122111210.1186/s12934-023-02172-5Metabolic engineering strategies for naringenin production enhancement in Streptomyces albidoflavus J1074Suhui Ye0Patricia Magadán-Corpas1Álvaro Pérez-Valero2Claudio J. Villar3Felipe Lombó4Research Group BIONUC (Biotechnology of Nutraceuticals and Bioactive Compounds), Departamento de Biología Funcional, Área de Microbiología, Universidad de OviedoResearch Group BIONUC (Biotechnology of Nutraceuticals and Bioactive Compounds), Departamento de Biología Funcional, Área de Microbiología, Universidad de OviedoResearch Group BIONUC (Biotechnology of Nutraceuticals and Bioactive Compounds), Departamento de Biología Funcional, Área de Microbiología, Universidad de OviedoResearch Group BIONUC (Biotechnology of Nutraceuticals and Bioactive Compounds), Departamento de Biología Funcional, Área de Microbiología, Universidad de OviedoResearch Group BIONUC (Biotechnology of Nutraceuticals and Bioactive Compounds), Departamento de Biología Funcional, Área de Microbiología, Universidad de OviedoAbstract Background Naringenin is an industrially relevant compound due to its multiple pharmaceutical properties as well as its central role in flavonoid biosynthesis. Results On our way to develop Streptomyces albidoflavus J1074 as a microbial cell factory for naringenin production, we have significantly increased the yields of this flavanone by combining various metabolic engineering strategies, fermentation strategies and genome editing approaches in a stepwise manner. Specifically, we have screened different cultivation media to identify the optimal production conditions and have investigated how the additive feeding of naringenin precursors influences the production. Furthermore, we have employed genome editing strategies to remove biosynthetic gene clusters (BGCs) associated with pathways that might compete with naringenin biosynthesis for malonyl-CoA precursors. Moreover, we have expressed MatBC, coding for a malonate transporter and an enzyme responsible for the conversion of malonate into malonyl-CoA, respectively, and have duplicated the naringenin BGC, further contributing to the production improvement. By combining all of these strategies, we were able to achieve a remarkable 375-fold increase (from 0.06 mg/L to 22.47 mg/L) in naringenin titers. Conclusion This work demonstrates the influence that fermentation conditions have over the final yield of a bioactive compound of interest and highlights various bottlenecks that affect production. Once such bottlenecks are identified, different strategies can be applied to overcome them, although the efficiencies of such strategies may vary and are difficult to predict.https://doi.org/10.1186/s12934-023-02172-5FlavonoidPolyphenolGenome editingFermentation optimizationMalonate |
| spellingShingle | Suhui Ye Patricia Magadán-Corpas Álvaro Pérez-Valero Claudio J. Villar Felipe Lombó Metabolic engineering strategies for naringenin production enhancement in Streptomyces albidoflavus J1074 Microbial Cell Factories Flavonoid Polyphenol Genome editing Fermentation optimization Malonate |
| title | Metabolic engineering strategies for naringenin production enhancement in Streptomyces albidoflavus J1074 |
| title_full | Metabolic engineering strategies for naringenin production enhancement in Streptomyces albidoflavus J1074 |
| title_fullStr | Metabolic engineering strategies for naringenin production enhancement in Streptomyces albidoflavus J1074 |
| title_full_unstemmed | Metabolic engineering strategies for naringenin production enhancement in Streptomyces albidoflavus J1074 |
| title_short | Metabolic engineering strategies for naringenin production enhancement in Streptomyces albidoflavus J1074 |
| title_sort | metabolic engineering strategies for naringenin production enhancement in streptomyces albidoflavus j1074 |
| topic | Flavonoid Polyphenol Genome editing Fermentation optimization Malonate |
| url | https://doi.org/10.1186/s12934-023-02172-5 |
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