Paradigm of engineering recalcitrant non-model microorganism with dominant metabolic pathway as a biorefinery chassis

Abstract The development and implementation of microbial chassis cells have profound impacts on circular economy. Non-model bacterium Zymomonas mobilis is an excellent chassis owing to its extraordinary industrial characteristics. Here, the genome-scale metabolic model iZM516 is improved and updated...

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Main Authors: Xiongying Yan, Weiwei Bao, Yalun Wu, Chenyue Zhang, Zhitao Mao, Qianqian Yuan, Zhousheng Hu, Penghui He, Qiqun Peng, Mimi Hu, Binan Geng, Hongwu Ma, Shouwen Chen, Qiang Fei, Qiaoning He, Shihui Yang
Format: Article
Language:English
Published: Nature Portfolio 2024-11-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-024-54897-5
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author Xiongying Yan
Weiwei Bao
Yalun Wu
Chenyue Zhang
Zhitao Mao
Qianqian Yuan
Zhousheng Hu
Penghui He
Qiqun Peng
Mimi Hu
Binan Geng
Hongwu Ma
Shouwen Chen
Qiang Fei
Qiaoning He
Shihui Yang
author_facet Xiongying Yan
Weiwei Bao
Yalun Wu
Chenyue Zhang
Zhitao Mao
Qianqian Yuan
Zhousheng Hu
Penghui He
Qiqun Peng
Mimi Hu
Binan Geng
Hongwu Ma
Shouwen Chen
Qiang Fei
Qiaoning He
Shihui Yang
author_sort Xiongying Yan
collection DOAJ
description Abstract The development and implementation of microbial chassis cells have profound impacts on circular economy. Non-model bacterium Zymomonas mobilis is an excellent chassis owing to its extraordinary industrial characteristics. Here, the genome-scale metabolic model iZM516 is improved and updated by integrating enzyme constraints to simulate the dynamics of flux distribution and guide pathway design. We show that the innate dominant ethanol pathway of Z. mobilis restricts the titer and rate of these biochemicals. A dominant-metabolism compromised intermediate-chassis (DMCI) strategy is then developed through introducing low toxicity but cofactor imbalanced 2,3-butanediol pathway, and a recombinant D-lactate producer is constructed to produce more than 140.92 g/L and 104.6 g/L D-lactate (yield > 0.97 g/g) from glucose and corncob residue hydrolysate, respectively. Additionally, techno-economic analysis (TEA) and life cycle assessment (LCA) demonstrate the commercialization feasibility and greenhouse gas reduction capability of lignocellulosic D-lactate. This work thus establishes a paradigm for engineering recalcitrant microorganisms as biorefinery chassis.
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spelling doaj-art-169ffd0e773c4e6b9297a1550bde0d652024-12-01T12:35:07ZengNature PortfolioNature Communications2041-17232024-11-0115111510.1038/s41467-024-54897-5Paradigm of engineering recalcitrant non-model microorganism with dominant metabolic pathway as a biorefinery chassisXiongying Yan0Weiwei Bao1Yalun Wu2Chenyue Zhang3Zhitao Mao4Qianqian Yuan5Zhousheng Hu6Penghui He7Qiqun Peng8Mimi Hu9Binan Geng10Hongwu Ma11Shouwen Chen12Qiang Fei13Qiaoning He14Shihui Yang15State Key Laboratory of Biocatalysis and Enzyme Engineering, Environmental Microbial Technology Center of Hubei Province, and School of Life Sciences, Hubei UniversityState Key Laboratory of Biocatalysis and Enzyme Engineering, Environmental Microbial Technology Center of Hubei Province, and School of Life Sciences, Hubei UniversityState Key Laboratory of Biocatalysis and Enzyme Engineering, Environmental Microbial Technology Center of Hubei Province, and School of Life Sciences, Hubei UniversityXi’an Key Laboratory of C1 Compound Bioconversion Technology, School of Chemical Engineering and Technology, Xi’an Jiaotong UniversityBiodesign Center, Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of SciencesBiodesign Center, Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of SciencesState Key Laboratory of Biocatalysis and Enzyme Engineering, Environmental Microbial Technology Center of Hubei Province, and School of Life Sciences, Hubei UniversityState Key Laboratory of Biocatalysis and Enzyme Engineering, Environmental Microbial Technology Center of Hubei Province, and School of Life Sciences, Hubei UniversityState Key Laboratory of Biocatalysis and Enzyme Engineering, Environmental Microbial Technology Center of Hubei Province, and School of Life Sciences, Hubei UniversityState Key Laboratory of Biocatalysis and Enzyme Engineering, Environmental Microbial Technology Center of Hubei Province, and School of Life Sciences, Hubei UniversityState Key Laboratory of Biocatalysis and Enzyme Engineering, Environmental Microbial Technology Center of Hubei Province, and School of Life Sciences, Hubei UniversityBiodesign Center, Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of SciencesState Key Laboratory of Biocatalysis and Enzyme Engineering, Environmental Microbial Technology Center of Hubei Province, and School of Life Sciences, Hubei UniversityXi’an Key Laboratory of C1 Compound Bioconversion Technology, School of Chemical Engineering and Technology, Xi’an Jiaotong UniversityState Key Laboratory of Biocatalysis and Enzyme Engineering, Environmental Microbial Technology Center of Hubei Province, and School of Life Sciences, Hubei UniversityState Key Laboratory of Biocatalysis and Enzyme Engineering, Environmental Microbial Technology Center of Hubei Province, and School of Life Sciences, Hubei UniversityAbstract The development and implementation of microbial chassis cells have profound impacts on circular economy. Non-model bacterium Zymomonas mobilis is an excellent chassis owing to its extraordinary industrial characteristics. Here, the genome-scale metabolic model iZM516 is improved and updated by integrating enzyme constraints to simulate the dynamics of flux distribution and guide pathway design. We show that the innate dominant ethanol pathway of Z. mobilis restricts the titer and rate of these biochemicals. A dominant-metabolism compromised intermediate-chassis (DMCI) strategy is then developed through introducing low toxicity but cofactor imbalanced 2,3-butanediol pathway, and a recombinant D-lactate producer is constructed to produce more than 140.92 g/L and 104.6 g/L D-lactate (yield > 0.97 g/g) from glucose and corncob residue hydrolysate, respectively. Additionally, techno-economic analysis (TEA) and life cycle assessment (LCA) demonstrate the commercialization feasibility and greenhouse gas reduction capability of lignocellulosic D-lactate. This work thus establishes a paradigm for engineering recalcitrant microorganisms as biorefinery chassis.https://doi.org/10.1038/s41467-024-54897-5
spellingShingle Xiongying Yan
Weiwei Bao
Yalun Wu
Chenyue Zhang
Zhitao Mao
Qianqian Yuan
Zhousheng Hu
Penghui He
Qiqun Peng
Mimi Hu
Binan Geng
Hongwu Ma
Shouwen Chen
Qiang Fei
Qiaoning He
Shihui Yang
Paradigm of engineering recalcitrant non-model microorganism with dominant metabolic pathway as a biorefinery chassis
Nature Communications
title Paradigm of engineering recalcitrant non-model microorganism with dominant metabolic pathway as a biorefinery chassis
title_full Paradigm of engineering recalcitrant non-model microorganism with dominant metabolic pathway as a biorefinery chassis
title_fullStr Paradigm of engineering recalcitrant non-model microorganism with dominant metabolic pathway as a biorefinery chassis
title_full_unstemmed Paradigm of engineering recalcitrant non-model microorganism with dominant metabolic pathway as a biorefinery chassis
title_short Paradigm of engineering recalcitrant non-model microorganism with dominant metabolic pathway as a biorefinery chassis
title_sort paradigm of engineering recalcitrant non model microorganism with dominant metabolic pathway as a biorefinery chassis
url https://doi.org/10.1038/s41467-024-54897-5
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