Journal article
Butyrate as a growth factor of Clostridium acetobutylicum
Metabolic engineering, Vol.86, pp.194-207
11/2024
DOI: 10.1016/j.ymben.2024.10.005
PMID: 39413987
Abstract
The butyrate biosynthetic pathway not only contributes to electron management and energy generation in butyrate forming bacteria, but also confers evolutionary advantages to the host by inhibiting the growth of surrounding butyrate-sensitive microbes. While high butyrate levels induce toxic stress, effects of non-toxic levels on cell growth, health, metabolism, and sporulation remain unclear. Here, we show that butyrate stimulates cellular processes of Clostridium acetobutylicum, a model butyrate forming Firmicute. First, we deleted the 3-hydroxybutyryl-CoA dehydrogenase gene (hbd) from the C. acetobutylicum chromosome to eliminate the butyrate synthetic pathway and thus butyrate formation. A xylose inducible Cas9 cassette was chromosomally integrated and utilized for the one-step markerless gene deletions. Non-toxic butyrate levels significantly affected growth, health, and sporulation of C. acetobutylicum. Upon deleting spo0A, the gene of the master regulator of sporulation, Spo0A, and followed by butyrate addition experiments, we conclude that butyrate affects cellular metabolism through both Spo0A-dependent and independent mechanisms. We also deleted the hbd gene from the chromosome of the asporogenous C. acetobutylicum M5 strain lacking the pSOL1 plasmid to examine the potential involvement of pSOL1 genes on the observed butyrate effects. Addition of the precursor of butyrate biosynthesis crotonate to the hbd deficient M5 strain was used to probe the role of butyrate biosynthesis pathway in electron and metabolic fluxes. Finally, we found that butyrate addition can enhance the growth of the non-butyrate forming Clostridium saccharolyticum. Our data suggest that butyrate functions as a stimulator of cellular processes, like a growth factor, in C. acetobutylicum and potentially evolutionarily related Clostridium organisms.
Details
- Title: Subtitle
- Butyrate as a growth factor of Clostridium acetobutylicum
- Creators
- Hyeongmin Seo - University of DelawareSofia H Capece - University of DelawareJohn D Hill - University of DelawareJonathan K Otten - University of DelawareEleftherios T Papoutsakis - University of Delaware
- Resource Type
- Journal article
- Publication Details
- Metabolic engineering, Vol.86, pp.194-207
- DOI
- 10.1016/j.ymben.2024.10.005
- PMID
- 39413987
- NLM abbreviation
- Metab Eng
- ISSN
- 1096-7176
- eISSN
- 1096-7184
- Publisher
- ACADEMIC PRESS INC ELSEVIER SCIENCE
- Grant note
- U.S. Department of Energy, Advanced Research Projects Agency-Energy (ARPA-E) ECO Syn Bio: DE-AR0001505 U.S. Department of Education GAANN Fellowship: P200A210065
This work was financially supported by the U.S. Department of Energy, Advanced Research Projects Agency-Energy (ARPA-E) ECO Syn Bio under award number #DE-AR0001505. JDH was supported in part by the U.S. Department of Education GAANN Fellowship under grant P200A210065. Illustrations were created with BioRender.com .
- Language
- English
- Electronic publication date
- 10/14/2024
- Date published
- 11/2024
- Academic Unit
- Chemical and Biochemical Engineering
- Record Identifier
- 9984736599902771
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