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MftG is crucial for ethanol metabolism of mycobacteria by linking mycofactocin oxidation to respiration
Open accessPreprint — published as 10.7554/elife.97559.4 · Paper page
Abstract
Mycofactocin is a redox cofactor essential for the alcohol metabolism of mycobacteria.. While the biosynthesis of mycofactocin is well established, the gene mftG , which encodes an oxidoreductase of the glucose-methanol-choline superfamily, remained functionally uncharacterized. Here, we show that MftG enzymes are almost exclusively found in genomes containing mycofactocin biosynthetic genes and are present in 75% of organisms harboring these genes. Gene deletion experiments in Mycolicibacterium smegmatis demonstrated a growth defect of the Δ mftG mutant on ethanol as a carbon source, accompanied by an arrest of cell division reminiscent of mild starvation. Investigation of carbon and cofactor metabolism implied a defect in mycofactocin reoxidation. Cell-free enzyme assays and respirometry using isolated cell membranes indicated that MftG acts as a mycofactocin dehydrogenase shuttling electrons toward the respiratory chain. Transcriptomics studies also indicated remodeling of redox metabolism to compensate for a shortage of redox equivalents. In conclusion, this work closes an important knowledge gap concerning the mycofactocin system and adds a new pathway to the intricate web of redox reactions governing the metabolism of mycobacteria.
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Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764
Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria
Cook, G. M., Hards, K., Vilchèze, C., Hartman, T., & Berney, M. (2014) · Microbiology Spectrum · doi:10.1128/microbiolspec.mgm2-0015-2013 · Cited by 212
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Metadata
- Authors
- Graça, A. P., Nikitushkin, V., Ellerhorst, M., Vilhena, C., Klassert, T. E., Starick, A., Siemers, M., Al-Jammal, W. K., Vilotijevic, I., Slevogt, H., Papenfort, K., & Lackner, G.
- Affiliations
- Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e. V. - Hans-Knöll-Institut (HKI) (DE)
- Medizinische Hochschule Hannover (DE)
- Friedrich Schiller University Jena (DE)
- Corresponding author
- Lackner, Gerald
- ORCID
- Venue
- eLife
- Publisher
- openRxiv
- Published
- 2024-03-28
- Volume
- 13
- ISSN
- 2050-084X (ISSN-L)
- OpenAlex
- W4406929589
- Cited by
- 3
- References
- 2
- Citations by year
- 2025: 3
- FWCI
- 0.91
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- Funders
- Carl-Zeiss-Stiftung
- Freistaat Thüringen (2019 FGI 0003)
- Deutscher Akademischer Austauschdienst
- Deutsche Forschungsgemeinschaft (EXC 2051—, 390713860)
- Leibniz-Gemeinschaft
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial metabolism and enzyme function
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Life Sciences › Immunology and Microbiology › Applied Microbiology and Biotechnology › Microbial Natural Products and Biosynthesis
- Keywords
- alcohol metabolism, mycobacteria, glucose-methanol-choline oxidoreductase, redox cofactors, Mycolicibacterium smegmatis, redox metabolism, cell division arrest, carbon source utilization
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