Lipid membrane remodeling and metabolic response during isobutanol and ethanol exposure in Zymomonas mobilis
Abstract
Abstract Background Recent engineering efforts have targeted the ethanologenic bacterium Zymomonas mobilis for isobutanol production. However, significant hurdles remain due this organism’s vulnerability to isobutanol toxicity, adversely affecting its growth and productivity. The limited understanding of the physiological impacts of isobutanol on Z. mobilis constrains our ability to overcome these production barriers. Results We utilized a systems-level approach comprising LC–MS/MS-based lipidomics, metabolomics, and shotgun proteomics, to investigate how exposure to ethanol and isobutanol impact the lipid membrane composition and overall physiology of Z. mobilis . Our analysis revealed significant and distinct alterations in membrane phospholipid and fatty acid composition resulting from ethanol and isobutanol exposure. Notably, ethanol exposure increased membrane cyclopropane fatty acid content and expression of cyclopropane fatty acid (CFA) synthase. Surprisingly, isobutanol decreased cyclopropane fatty acid content despite robust upregulation of CFA synthase. Overexpression of the native Z. mobilis’ CFA synthase increased cyclopropane fatty acid content in all phospholipid classes and was associated with a significant improvement in growth rates in the presence of added ethanol and isobutanol. Heterologous expression of CFA synthase from Clostridium acetobutylicum resulted in a near complete replacement of unsaturated fatty acids with cyclopropane fatty acids, affecting all lipid classes. However, this did notmore »
- Authors:
- Publication Date:
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 2283103
- Grant/Contract Number:
- SC0018409
- Resource Type:
- Published Article
- Journal Name:
- Biotechnology for Biofuels and Bioproducts
- Additional Journal Information:
- Journal Name: Biotechnology for Biofuels and Bioproducts Journal Volume: 17 Journal Issue: 1; Journal ID: ISSN 2731-3654
- Publisher:
- Springer Science + Business Media
- Country of Publication:
- United Kingdom
- Language:
- English
Citation Formats
Rivera Vazquez, Julio, Trujillo, Edna, Williams, Jonathan, She, Fukang, Getahun, Fitsum, Callaghan, Melanie M., Coon, Joshua J., and Amador-Noguez, Daniel. Lipid membrane remodeling and metabolic response during isobutanol and ethanol exposure in Zymomonas mobilis. United Kingdom: N. p., 2024.
Web. doi:10.1186/s13068-023-02450-9.
Rivera Vazquez, Julio, Trujillo, Edna, Williams, Jonathan, She, Fukang, Getahun, Fitsum, Callaghan, Melanie M., Coon, Joshua J., & Amador-Noguez, Daniel. Lipid membrane remodeling and metabolic response during isobutanol and ethanol exposure in Zymomonas mobilis. United Kingdom. https://doi.org/10.1186/s13068-023-02450-9
Rivera Vazquez, Julio, Trujillo, Edna, Williams, Jonathan, She, Fukang, Getahun, Fitsum, Callaghan, Melanie M., Coon, Joshua J., and Amador-Noguez, Daniel. Sun .
"Lipid membrane remodeling and metabolic response during isobutanol and ethanol exposure in Zymomonas mobilis". United Kingdom. https://doi.org/10.1186/s13068-023-02450-9.
@article{osti_2283103,
title = {Lipid membrane remodeling and metabolic response during isobutanol and ethanol exposure in Zymomonas mobilis},
author = {Rivera Vazquez, Julio and Trujillo, Edna and Williams, Jonathan and She, Fukang and Getahun, Fitsum and Callaghan, Melanie M. and Coon, Joshua J. and Amador-Noguez, Daniel},
abstractNote = {Abstract Background Recent engineering efforts have targeted the ethanologenic bacterium Zymomonas mobilis for isobutanol production. However, significant hurdles remain due this organism’s vulnerability to isobutanol toxicity, adversely affecting its growth and productivity. The limited understanding of the physiological impacts of isobutanol on Z. mobilis constrains our ability to overcome these production barriers. Results We utilized a systems-level approach comprising LC–MS/MS-based lipidomics, metabolomics, and shotgun proteomics, to investigate how exposure to ethanol and isobutanol impact the lipid membrane composition and overall physiology of Z. mobilis . Our analysis revealed significant and distinct alterations in membrane phospholipid and fatty acid composition resulting from ethanol and isobutanol exposure. Notably, ethanol exposure increased membrane cyclopropane fatty acid content and expression of cyclopropane fatty acid (CFA) synthase. Surprisingly, isobutanol decreased cyclopropane fatty acid content despite robust upregulation of CFA synthase. Overexpression of the native Z. mobilis’ CFA synthase increased cyclopropane fatty acid content in all phospholipid classes and was associated with a significant improvement in growth rates in the presence of added ethanol and isobutanol. Heterologous expression of CFA synthase from Clostridium acetobutylicum resulted in a near complete replacement of unsaturated fatty acids with cyclopropane fatty acids, affecting all lipid classes. However, this did not translate to improved growth rates under isobutanol exposure. Correlating with its greater susceptibility to isobutanol, Z. mobilis exhibited more pronounced alterations in its proteome, metabolome, and overall cell morphology—including cell swelling and formation of intracellular protein aggregates —when exposed to isobutanol compared to ethanol. Isobutanol triggered a broad stress response marked by the upregulation of heat shock proteins, efflux transporters, DNA repair systems, and the downregulation of cell motility proteins. Isobutanol also elicited widespread dysregulation of Z. mobilis ’ primary metabolism evidenced by increased levels of nucleotide degradation intermediates and the depletion of biosynthetic and glycolytic intermediates. Conclusions This study provides a comprehensive, systems-level evaluation of the impact of ethanol and isobutanol exposure on the lipid membrane composition and overall physiology of Z. mobilis . These findings will guide engineering of Z. mobilis towards the creation of isobutanol-tolerant strains that can serve as robust platforms for the industrial production of isobutanol from lignocellulosic sugars.},
doi = {10.1186/s13068-023-02450-9},
journal = {Biotechnology for Biofuels and Bioproducts},
number = 1,
volume = 17,
place = {United Kingdom},
year = {Sun Jan 28 00:00:00 EST 2024},
month = {Sun Jan 28 00:00:00 EST 2024}
}
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