A citric acid cycle-deficient Escherichia coli as an efficient chassis for aerobic fermentations.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
15 Mar 2024
15 Mar 2024
Historique:
received:
21
04
2023
accepted:
05
03
2024
medline:
18
3
2024
pubmed:
16
3
2024
entrez:
16
3
2024
Statut:
epublish
Résumé
Tricarboxylic acid cycle (TCA cycle) plays an important role for aerobic growth of heterotrophic bacteria. Theoretically, eliminating TCA cycle would decrease carbon dissipation and facilitate chemicals biosynthesis. Here, we construct an E. coli strain without a functional TCA cycle that can serve as a versatile chassis for chemicals biosynthesis. We first use adaptive laboratory evolution to recover aerobic growth in minimal medium of TCA cycle-deficient E. coli. Inactivation of succinate dehydrogenase is a key event in the evolutionary trajectory. Supply of succinyl-CoA is identified as the growth limiting factor. By replacing endogenous succinyl-CoA dependent enzymes, we obtain an optimized TCA cycle-deficient E. coli strain. As a proof of concept, the strain is engineered for high-yield production of four separate products. This work enhances our understanding of the role of the TCA cycle in E. coli metabolism and demonstrates the advantages of using TCA cycle-deficient E. coli strain for biotechnological applications.
Identifiants
pubmed: 38491007
doi: 10.1038/s41467-024-46655-4
pii: 10.1038/s41467-024-46655-4
pmc: PMC10943122
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2372Subventions
Organisme : Ministry of Science and Technology of the People's Republic of China (Chinese Ministry of Science and Technology)
ID : 2022YFC2106000
Organisme : Ministry of Science and Technology of the People's Republic of China (Chinese Ministry of Science and Technology)
ID : 2018YFA0901400
Informations de copyright
© 2024. The Author(s).
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