Systems metabolic engineering of Escherichia coli for hyper-production of 5‑aminolevulinic acid
Abstract Background 5-Aminolevulinic acid (5-ALA) is a promising biostimulant, feed nutrient, and photodynamic drug with wide applications in modern agriculture and therapy. Although microbial production of 5-ALA has been improved realized by using metabolic engineering strategies during the past fe...
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| Format: | Article |
| Language: | English |
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BMC
2023-02-01
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| Series: | Biotechnology for Biofuels and Bioproducts |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13068-023-02280-9 |
| _version_ | 1797789855486312448 |
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| author | Wei Pu Jiuzhou Chen Yingyu Zhou Huamin Qiu Tuo Shi Wenjuan Zhou Xuan Guo Ningyun Cai Zijian Tan Jiao Liu Jinhui Feng Yu Wang Ping Zheng Jibin Sun |
| author_facet | Wei Pu Jiuzhou Chen Yingyu Zhou Huamin Qiu Tuo Shi Wenjuan Zhou Xuan Guo Ningyun Cai Zijian Tan Jiao Liu Jinhui Feng Yu Wang Ping Zheng Jibin Sun |
| author_sort | Wei Pu |
| collection | DOAJ |
| description | Abstract Background 5-Aminolevulinic acid (5-ALA) is a promising biostimulant, feed nutrient, and photodynamic drug with wide applications in modern agriculture and therapy. Although microbial production of 5-ALA has been improved realized by using metabolic engineering strategies during the past few years, there is still a gap between the present production level and the requirement of industrialization. Results In this study, pathway, protein, and cellular engineering strategies were systematically employed to construct an industrially competitive 5-ALA producing Escherichia coli. Pathways involved in precursor supply and product degradation were regulated by gene overexpression and synthetic sRNA-based repression to channel metabolic flux to 5-ALA biosynthesis. 5-ALA synthase was rationally engineered to release the inhibition of heme and improve the catalytic activity. 5-ALA transport and antioxidant defense systems were targeted to enhance cellular tolerance to intra- and extra-cellular 5-ALA. The final engineered strain produced 30.7 g/L of 5-ALA in bioreactors with a productivity of 1.02 g/L/h and a yield of 0.532 mol/mol glucose, represent a new record of 5-ALA bioproduction. Conclusions An industrially competitive 5-ALA producing E. coli strain was constructed with the metabolic engineering strategies at multiple layers (protein, pathway, and cellular engineering), and the strategies here can be useful for developing industrial-strength strains for biomanufacturing. |
| first_indexed | 2024-03-13T01:56:28Z |
| format | Article |
| id | doaj.art-88fa2651067c49288dc02b462e12214f |
| institution | Directory Open Access Journal |
| issn | 2731-3654 |
| language | English |
| last_indexed | 2024-03-13T01:56:28Z |
| publishDate | 2023-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Biotechnology for Biofuels and Bioproducts |
| spelling | doaj.art-88fa2651067c49288dc02b462e12214f2023-07-02T11:10:13ZengBMCBiotechnology for Biofuels and Bioproducts2731-36542023-02-0116111610.1186/s13068-023-02280-9Systems metabolic engineering of Escherichia coli for hyper-production of 5‑aminolevulinic acidWei Pu0Jiuzhou Chen1Yingyu Zhou2Huamin Qiu3Tuo Shi4Wenjuan Zhou5Xuan Guo6Ningyun Cai7Zijian Tan8Jiao Liu9Jinhui Feng10Yu Wang11Ping Zheng12Jibin Sun13Key Laboratory of Systems Microbial Biotechnology, Chinese Academy of Sciences, Tianjin Institute of Industrial BiotechnologyKey Laboratory of Systems Microbial Biotechnology, Chinese Academy of Sciences, Tianjin Institute of Industrial BiotechnologyKey Laboratory of Systems Microbial Biotechnology, Chinese Academy of Sciences, Tianjin Institute of Industrial BiotechnologyKey Laboratory of Systems Microbial Biotechnology, Chinese Academy of Sciences, Tianjin Institute of Industrial BiotechnologyKey Laboratory of Systems Microbial Biotechnology, Chinese Academy of Sciences, Tianjin Institute of Industrial BiotechnologyKey Laboratory of Systems Microbial Biotechnology, Chinese Academy of Sciences, Tianjin Institute of Industrial BiotechnologyKey Laboratory of Systems Microbial Biotechnology, Chinese Academy of Sciences, Tianjin Institute of Industrial BiotechnologyKey Laboratory of Systems Microbial Biotechnology, Chinese Academy of Sciences, Tianjin Institute of Industrial BiotechnologyKey Laboratory of Systems Microbial Biotechnology, Chinese Academy of Sciences, Tianjin Institute of Industrial BiotechnologyKey Laboratory of Systems Microbial Biotechnology, Chinese Academy of Sciences, Tianjin Institute of Industrial BiotechnologyKey Laboratory of Systems Microbial Biotechnology, Chinese Academy of Sciences, Tianjin Institute of Industrial BiotechnologyKey Laboratory of Systems Microbial Biotechnology, Chinese Academy of Sciences, Tianjin Institute of Industrial BiotechnologyKey Laboratory of Systems Microbial Biotechnology, Chinese Academy of Sciences, Tianjin Institute of Industrial BiotechnologyKey Laboratory of Systems Microbial Biotechnology, Chinese Academy of Sciences, Tianjin Institute of Industrial BiotechnologyAbstract Background 5-Aminolevulinic acid (5-ALA) is a promising biostimulant, feed nutrient, and photodynamic drug with wide applications in modern agriculture and therapy. Although microbial production of 5-ALA has been improved realized by using metabolic engineering strategies during the past few years, there is still a gap between the present production level and the requirement of industrialization. Results In this study, pathway, protein, and cellular engineering strategies were systematically employed to construct an industrially competitive 5-ALA producing Escherichia coli. Pathways involved in precursor supply and product degradation were regulated by gene overexpression and synthetic sRNA-based repression to channel metabolic flux to 5-ALA biosynthesis. 5-ALA synthase was rationally engineered to release the inhibition of heme and improve the catalytic activity. 5-ALA transport and antioxidant defense systems were targeted to enhance cellular tolerance to intra- and extra-cellular 5-ALA. The final engineered strain produced 30.7 g/L of 5-ALA in bioreactors with a productivity of 1.02 g/L/h and a yield of 0.532 mol/mol glucose, represent a new record of 5-ALA bioproduction. Conclusions An industrially competitive 5-ALA producing E. coli strain was constructed with the metabolic engineering strategies at multiple layers (protein, pathway, and cellular engineering), and the strategies here can be useful for developing industrial-strength strains for biomanufacturing.https://doi.org/10.1186/s13068-023-02280-95‑Aminolevulinic acidSystems metabolic engineeringEscherichia coliSynthetic sRNAAntioxidant defense system |
| spellingShingle | Wei Pu Jiuzhou Chen Yingyu Zhou Huamin Qiu Tuo Shi Wenjuan Zhou Xuan Guo Ningyun Cai Zijian Tan Jiao Liu Jinhui Feng Yu Wang Ping Zheng Jibin Sun Systems metabolic engineering of Escherichia coli for hyper-production of 5‑aminolevulinic acid Biotechnology for Biofuels and Bioproducts 5‑Aminolevulinic acid Systems metabolic engineering Escherichia coli Synthetic sRNA Antioxidant defense system |
| title | Systems metabolic engineering of Escherichia coli for hyper-production of 5‑aminolevulinic acid |
| title_full | Systems metabolic engineering of Escherichia coli for hyper-production of 5‑aminolevulinic acid |
| title_fullStr | Systems metabolic engineering of Escherichia coli for hyper-production of 5‑aminolevulinic acid |
| title_full_unstemmed | Systems metabolic engineering of Escherichia coli for hyper-production of 5‑aminolevulinic acid |
| title_short | Systems metabolic engineering of Escherichia coli for hyper-production of 5‑aminolevulinic acid |
| title_sort | systems metabolic engineering of escherichia coli for hyper production of 5 aminolevulinic acid |
| topic | 5‑Aminolevulinic acid Systems metabolic engineering Escherichia coli Synthetic sRNA Antioxidant defense system |
| url | https://doi.org/10.1186/s13068-023-02280-9 |
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