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Systems metabolic engineering of Escherichia coli for hyper-production of 5‑aminolevulinic acid
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,...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9951541/ https://www.ncbi.nlm.nih.gov/pubmed/36829220 http://dx.doi.org/10.1186/s13068-023-02280-9 |
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author | Pu, Wei Chen, Jiuzhou Zhou, Yingyu Qiu, Huamin Shi, Tuo Zhou, Wenjuan Guo, Xuan Cai, Ningyun Tan, Zijian Liu, Jiao Feng, Jinhui Wang, Yu Zheng, Ping Sun, Jibin |
author_facet | Pu, Wei Chen, Jiuzhou Zhou, Yingyu Qiu, Huamin Shi, Tuo Zhou, Wenjuan Guo, Xuan Cai, Ningyun Tan, Zijian Liu, Jiao Feng, Jinhui Wang, Yu Zheng, Ping Sun, Jibin |
author_sort | Pu, Wei |
collection | PubMed |
description | 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13068-023-02280-9. |
format | Online Article Text |
id | pubmed-9951541 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-99515412023-02-25 Systems metabolic engineering of Escherichia coli for hyper-production of 5‑aminolevulinic acid Pu, Wei Chen, Jiuzhou Zhou, Yingyu Qiu, Huamin Shi, Tuo Zhou, Wenjuan Guo, Xuan Cai, Ningyun Tan, Zijian Liu, Jiao Feng, Jinhui Wang, Yu Zheng, Ping Sun, Jibin Biotechnol Biofuels Bioprod Research 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13068-023-02280-9. BioMed Central 2023-02-24 /pmc/articles/PMC9951541/ /pubmed/36829220 http://dx.doi.org/10.1186/s13068-023-02280-9 Text en © The Author(s) 2023, corrected publication 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Pu, Wei Chen, Jiuzhou Zhou, Yingyu Qiu, Huamin Shi, Tuo Zhou, Wenjuan Guo, Xuan Cai, Ningyun Tan, Zijian Liu, Jiao Feng, Jinhui Wang, Yu Zheng, Ping Sun, Jibin Systems metabolic engineering of Escherichia coli for hyper-production of 5‑aminolevulinic acid |
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 | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9951541/ https://www.ncbi.nlm.nih.gov/pubmed/36829220 http://dx.doi.org/10.1186/s13068-023-02280-9 |
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