Tailoring Corynebacterium glutamicum towards increased malonyl-CoA availability for efficient synthesis of the plant pentaketide noreugenin.
Acetyl-CoA carboxylase
Corynebacterium glutamicum
Malonyl-CoA
Metabolic engineering
Noreugenin
Journal
Microbial cell factories
ISSN: 1475-2859
Titre abrégé: Microb Cell Fact
Pays: England
ID NLM: 101139812
Informations de publication
Date de publication:
11 Apr 2019
11 Apr 2019
Historique:
received:
02
03
2019
accepted:
03
04
2019
entrez:
13
4
2019
pubmed:
13
4
2019
medline:
27
6
2019
Statut:
epublish
Résumé
In the last years, different biotechnologically relevant microorganisms have been engineered for the synthesis of plant polyphenols such as flavonoids and stilbenes. However, low intracellular availability of malonyl-CoA as essential precursor for most plant polyphenols of interest is regarded as the decisive bottleneck preventing high product titers. In this study, Corynebacterium glutamicum, which emerged as promising cell factory for plant polyphenol production, was tailored by rational metabolic engineering towards providing significantly more malonyl-CoA for product synthesis. This was achieved by improving carbon source uptake, transcriptional deregulation of accBC and accD1 encoding the two subunits of the acetyl-CoA carboxylase (ACC), reduced flux into the tricarboxylic acid (TCA) cycle, and elimination of anaplerotic carboxylation of pyruvate. The constructed strains were used for the synthesis of the pharmacologically interesting plant pentaketide noreugenin, which is produced by plants such as Aloe arborescens from five molecules of malonyl-CoA. In this context, accumulation of the C The best strain C. glutamicum Nor2 C5 mufasO
Sections du résumé
BACKGROUND
BACKGROUND
In the last years, different biotechnologically relevant microorganisms have been engineered for the synthesis of plant polyphenols such as flavonoids and stilbenes. However, low intracellular availability of malonyl-CoA as essential precursor for most plant polyphenols of interest is regarded as the decisive bottleneck preventing high product titers.
RESULTS
RESULTS
In this study, Corynebacterium glutamicum, which emerged as promising cell factory for plant polyphenol production, was tailored by rational metabolic engineering towards providing significantly more malonyl-CoA for product synthesis. This was achieved by improving carbon source uptake, transcriptional deregulation of accBC and accD1 encoding the two subunits of the acetyl-CoA carboxylase (ACC), reduced flux into the tricarboxylic acid (TCA) cycle, and elimination of anaplerotic carboxylation of pyruvate. The constructed strains were used for the synthesis of the pharmacologically interesting plant pentaketide noreugenin, which is produced by plants such as Aloe arborescens from five molecules of malonyl-CoA. In this context, accumulation of the C
CONCLUSION
CONCLUSIONS
The best strain C. glutamicum Nor2 C5 mufasO
Identifiants
pubmed: 30975146
doi: 10.1186/s12934-019-1117-x
pii: 10.1186/s12934-019-1117-x
pmc: PMC6460773
doi:
Substances chimiques
Glycosides
0
Polyphenols
0
Malonyl Coenzyme A
524-14-1
Pyruvic Acid
8558G7RUTR
Acetyl-CoA Carboxylase
EC 6.4.1.2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
71Subventions
Organisme : Bioeconomy Science Center
ID : Grant no.: 325 - 400 002 13
Organisme : Helmholtz-Gemeinschaft
ID : Enabling Spaces Program
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