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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,...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
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.
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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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