Efficient De Novo Biosynthesis of Curcumin in Escherichia coli by Optimizing Pathway Modules and Increasing the Malonyl-CoA Supply

Curcumin is a natural phenylpropanoid compound with various biological activities and is widely used in food and pharmaceuticals. A de novo curcumin biosynthetic pathway was constructed in Escherichia coli BL21(DE3). Optimization of the curcumin biosynthesis module achieved a curcumin titer of 26.8 ± 0.6 mg/L. Regulating the metabolic fluxes of the β-oxidation pathway and fatty acid elongation cycle and blocking the endogenous malonyl-CoA consumption pathway increased the titer to 113.6 ± 7.1 mg/L. Knockout of endogenous curcumin reductase (curA) and intermediate product detoxification by heterologous expression of the solvent-resistant pump (srpB) increased the titer to 137.5 ± 3.0 mg/L. A 5 L pilot-scale fermentation, using a three-stage pH alternation strategy, increased the titer to 696.2 ± 20.9 mg/L, 178.5-fold higher than the highest curcumin titer from de novo biosynthesis previously reported, thereby laying the foundation for efficient biosynthesis of curcumin and its derivatives.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:72

Enthalten in:

Journal of agricultural and food chemistry - 72(2024), 1 vom: 10. Jan., Seite 566-576

Sprache:

Englisch

Beteiligte Personen:

Chen, Jianbin [VerfasserIn]
Wang, Weigao [VerfasserIn]
Wang, Lian [VerfasserIn]
Wang, Huijing [VerfasserIn]
Hu, MingLong [VerfasserIn]
Zhou, Jingwen [VerfasserIn]
Du, Guocheng [VerfasserIn]
Zeng, Weizhu [VerfasserIn]

Links:

Volltext

Themen:

524-14-1
Curcumin
Escherichia coli Proteins
FadR
IT942ZTH98
Journal Article
Linker
Malonyl Coenzyme A
Malonyl-CoA
PH optimization

Anmerkungen:

Date Completed 11.01.2024

Date Revised 11.01.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1021/acs.jafc.3c07379

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM366447300