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  Engineering new-to-nature biochemical conversions by combining fermentative metabolism with respiratory modules

Schulz-Mirbach, H. A. M., Kruesemann, J. L., Andreadaki, T., Nerlich, J. N., Mavrothalassiti, E., Boecker, S., et al. (2024). Engineering new-to-nature biochemical conversions by combining fermentative metabolism with respiratory modules. Nature Communications, 15(1): 6725. doi:10.1038/s41467-024-51029-x.

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Schulz-Mirbach, Helena Anna Maria1, Author           
Kruesemann, J. L.1, Author           
Andreadaki, T.1, Author           
Nerlich, Jana Natalie2, Author
Mavrothalassiti, E.3, Author           
Boecker, Simon2, Author
Schneider, Philipp2, Author
Weresow, M.1, Author           
Abdelwahab, Omar2, Author
Paczia, Nicole2, Author
Dronsella, B.1, Author           
Erb, Tobias J.2, Author
Bar-Even, A.1, Author                 
Klamt, Steffen2, Author
Lindner, S. N.1, Author           
Affiliations:
1Systems and Synthetic Metabolism, Max Planck Research Groups, Max Planck Institute of Molecular Plant Physiology, Max Planck Society, ou_2035297              
2external, ou_persistent22              
3Intercellular Macromolecular Transport, Department Köhler, Max Planck Institute of Molecular Plant Physiology, Max Planck Society, ou_3338335              

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 Abstract: Anaerobic microbial fermentations provide high product yields and are a cornerstone of industrial bio-based processes. However, the need for redox balancing limits the array of fermentable substrate-product combinations. To overcome this limitation, here we design an aerobic fermentative metabolism that allows the introduction of selected respiratory modules. These can use oxygen to re-balance otherwise unbalanced fermentations, hence achieving controlled respiro-fermentative growth. Following this design, we engineer and characterize an obligate fermentative Escherichia coli strain that aerobically ferments glucose to stoichiometric amounts of lactate. We then re-integrate the quinone-dependent glycerol 3-phosphate dehydrogenase and demonstrate glycerol fermentation to lactate while selectively transferring the surplus of electrons to the respiratory chain. To showcase the potential of this fermentation mode, we direct fermentative flux from glycerol towards isobutanol production. In summary, our design permits using oxygen to selectively re-balance fermentations. This concept is an advance freeing highly efficient microbial fermentation from the limitations imposed by traditional redox balancing.

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Language(s): eng - English
 Dates: 2024-08-072024-07
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1038/s41467-024-51029-x
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Title: Nature Communications
  Abbreviation : Nat. Commun.
Source Genre: Journal
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Publ. Info: London : Nature Publishing Group
Pages: 6725 Volume / Issue: 15 (1) Sequence Number: 6725 Start / End Page: - Identifier: ISSN: 2041-1723
CoNE: https://pure.mpg.de/cone/journals/resource/2041-1723