Deletion of genes linked to the C1-fixing gene cluster affects growth, by-products, and proteome of Clostridium autoethanogenum

Gas fermentation has emerged as a sustainable route to produce fuels and chemicals by recycling inexpensive one-carbon (C1) feedstocks from gaseous and solid waste using gas-fermenting microbes. Currently, acetogens that utilise the Wood-Ljungdahl pathway to convert carbon oxides (CO and CO2) into v...

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Main Authors: Ugochi Jennifer Nwaokorie, Kristina Reinmets, Lorena Azevedo de Lima, Pratik Rajendra Pawar, Kurshedaktar Majibullah Shaikh, Audrey Harris, Michael Köpke, Kaspar Valgepea
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-05-01
Series:Frontiers in Bioengineering and Biotechnology
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Online Access:https://www.frontiersin.org/articles/10.3389/fbioe.2023.1167892/full
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author Ugochi Jennifer Nwaokorie
Kristina Reinmets
Lorena Azevedo de Lima
Pratik Rajendra Pawar
Kurshedaktar Majibullah Shaikh
Audrey Harris
Michael Köpke
Kaspar Valgepea
author_facet Ugochi Jennifer Nwaokorie
Kristina Reinmets
Lorena Azevedo de Lima
Pratik Rajendra Pawar
Kurshedaktar Majibullah Shaikh
Audrey Harris
Michael Köpke
Kaspar Valgepea
author_sort Ugochi Jennifer Nwaokorie
collection DOAJ
description Gas fermentation has emerged as a sustainable route to produce fuels and chemicals by recycling inexpensive one-carbon (C1) feedstocks from gaseous and solid waste using gas-fermenting microbes. Currently, acetogens that utilise the Wood-Ljungdahl pathway to convert carbon oxides (CO and CO2) into valuable products are the most advanced biocatalysts for gas fermentation. However, our understanding of the functionalities of the genes involved in the C1-fixing gene cluster and its closely-linked genes is incomplete. Here, we investigate the role of two genes with unclear functions—hypothetical protein (hp; LABRINI_07945) and CooT nickel binding protein (nbp; LABRINI_07950)—directly adjacent and expressed at similar levels to the C1-fixing gene cluster in the gas-fermenting model-acetogen Clostridium autoethanogenum. Targeted deletion of either the hp or nbp gene using CRISPR/nCas9, and phenotypic characterisation in heterotrophic and autotrophic batch and autotrophic bioreactor continuous cultures revealed significant growth defects and altered by-product profiles for both ∆hp and ∆nbp strains. Variable effects of gene deletion on autotrophic batch growth on rich or minimal media suggest that both genes affect the utilisation of complex nutrients. Autotrophic chemostat cultures showed lower acetate and ethanol production rates and higher carbon flux to CO2 and biomass for both deletion strains. Additionally, proteome analysis revealed that disruption of either gene affects the expression of proteins of the C1-fixing gene cluster and ethanol synthesis pathways. Our work contributes to a better understanding of genotype-phenotype relationships in acetogens and offers engineering targets to improve carbon fixation efficiency in gas fermentation.
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spelling doaj-art-c8d03f33be564159bc2a137ea2ea806a2025-08-20T02:26:46ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852023-05-011110.3389/fbioe.2023.11678921167892Deletion of genes linked to the C1-fixing gene cluster affects growth, by-products, and proteome of Clostridium autoethanogenumUgochi Jennifer Nwaokorie0Kristina Reinmets1Lorena Azevedo de Lima2Pratik Rajendra Pawar3Kurshedaktar Majibullah Shaikh4Audrey Harris5Michael Köpke6Kaspar Valgepea7ERA Chair in Gas Fermentation Technologies, Institute of Technology, University of Tartu, Tartu, EstoniaERA Chair in Gas Fermentation Technologies, Institute of Technology, University of Tartu, Tartu, EstoniaERA Chair in Gas Fermentation Technologies, Institute of Technology, University of Tartu, Tartu, EstoniaERA Chair in Gas Fermentation Technologies, Institute of Technology, University of Tartu, Tartu, EstoniaERA Chair in Gas Fermentation Technologies, Institute of Technology, University of Tartu, Tartu, EstoniaLanzaTech Inc., Skokie, IL, United StatesLanzaTech Inc., Skokie, IL, United StatesERA Chair in Gas Fermentation Technologies, Institute of Technology, University of Tartu, Tartu, EstoniaGas fermentation has emerged as a sustainable route to produce fuels and chemicals by recycling inexpensive one-carbon (C1) feedstocks from gaseous and solid waste using gas-fermenting microbes. Currently, acetogens that utilise the Wood-Ljungdahl pathway to convert carbon oxides (CO and CO2) into valuable products are the most advanced biocatalysts for gas fermentation. However, our understanding of the functionalities of the genes involved in the C1-fixing gene cluster and its closely-linked genes is incomplete. Here, we investigate the role of two genes with unclear functions—hypothetical protein (hp; LABRINI_07945) and CooT nickel binding protein (nbp; LABRINI_07950)—directly adjacent and expressed at similar levels to the C1-fixing gene cluster in the gas-fermenting model-acetogen Clostridium autoethanogenum. Targeted deletion of either the hp or nbp gene using CRISPR/nCas9, and phenotypic characterisation in heterotrophic and autotrophic batch and autotrophic bioreactor continuous cultures revealed significant growth defects and altered by-product profiles for both ∆hp and ∆nbp strains. Variable effects of gene deletion on autotrophic batch growth on rich or minimal media suggest that both genes affect the utilisation of complex nutrients. Autotrophic chemostat cultures showed lower acetate and ethanol production rates and higher carbon flux to CO2 and biomass for both deletion strains. Additionally, proteome analysis revealed that disruption of either gene affects the expression of proteins of the C1-fixing gene cluster and ethanol synthesis pathways. Our work contributes to a better understanding of genotype-phenotype relationships in acetogens and offers engineering targets to improve carbon fixation efficiency in gas fermentation.https://www.frontiersin.org/articles/10.3389/fbioe.2023.1167892/fullgas fermentationacetogenCRISPR/Cas9genetic engineeringmetabolomicsproteomics
spellingShingle Ugochi Jennifer Nwaokorie
Kristina Reinmets
Lorena Azevedo de Lima
Pratik Rajendra Pawar
Kurshedaktar Majibullah Shaikh
Audrey Harris
Michael Köpke
Kaspar Valgepea
Deletion of genes linked to the C1-fixing gene cluster affects growth, by-products, and proteome of Clostridium autoethanogenum
Frontiers in Bioengineering and Biotechnology
gas fermentation
acetogen
CRISPR/Cas9
genetic engineering
metabolomics
proteomics
title Deletion of genes linked to the C1-fixing gene cluster affects growth, by-products, and proteome of Clostridium autoethanogenum
title_full Deletion of genes linked to the C1-fixing gene cluster affects growth, by-products, and proteome of Clostridium autoethanogenum
title_fullStr Deletion of genes linked to the C1-fixing gene cluster affects growth, by-products, and proteome of Clostridium autoethanogenum
title_full_unstemmed Deletion of genes linked to the C1-fixing gene cluster affects growth, by-products, and proteome of Clostridium autoethanogenum
title_short Deletion of genes linked to the C1-fixing gene cluster affects growth, by-products, and proteome of Clostridium autoethanogenum
title_sort deletion of genes linked to the c1 fixing gene cluster affects growth by products and proteome of clostridium autoethanogenum
topic gas fermentation
acetogen
CRISPR/Cas9
genetic engineering
metabolomics
proteomics
url https://www.frontiersin.org/articles/10.3389/fbioe.2023.1167892/full
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