Fermentative N-methylanthranilate production by engineered Corynebacterium glutamicum

Walter T, Al Medani N, Burgardt A, Cankar K, Ferrer L, Kerbs A, Lee J-H, Mindt M, Risse JM, Wendisch VF (2020)
Microorganisms 8: 866.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
 
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Abstract / Bemerkung
The N-functionalized amino acid N-methylanthranilate is an important precursor for bioactive compounds such as anticancer acridone alkaloids, the antinociceptive alkaloid O-isopropyl N-methylanthranilate, the flavor compound O-methyl-N-methylanthranilate, and as a building block for peptide-based drugs. Current chemical and biocatalytic synthetic routes to N-alkylated amino acids are often unprofitable and restricted to low yields or high costs through cofactor regeneration systems. Amino acid fermentation processes using the Gram-positive bacterium Corynebacterium glutamicum are operated industrially at the million tons per annum scale. Fermentative processes using C. glutamicum for N-alkylated amino acids based on an imine reductase have been developed, while N-alkylation of the aromatic amino acid anthranilate with S-adenosyl methionine as methyl-donor has not been described for this bacterium. After metabolic engineering for enhanced supply of anthranilate by channeling carbon flux into the shikimate pathway, preventing by-product formation and enhancing sugar uptake, heterologous expression of the gene anmt encoding anthranilate N-methyltransferase from Ruta graveolens resulted in production of N-methylanthranilate (NMA), which accumulated in the culture medium. Increased SAM regeneration by coexpression of the homologous adenosylhomocysteinase gene sahH improved N-methylanthranilate production. In a test bioreactor culture, the metabolically engineered C. glutamicum C1* strain produced NMA to a final titer of 0.5 g·L−1 with a volumetric productivity of 0.01 g·L−1·h−1 and a yield of 4.8 mg·g−1 glucose.
Stichworte
N-functionalized amines; N-methylanthranilate; Corynebacterium glutamicum; metabolic engineering; sustainable production of quinoline precursors; acridone; quinazoline alkaloid drugs
Erscheinungsjahr
2020
Zeitschriftentitel
Microorganisms
Band
8
Art.-Nr.
866
eISSN
2076-2607
Page URI
https://pub.uni-bielefeld.de/record/2943755

Zitieren

Walter T, Al Medani N, Burgardt A, et al. Fermentative N-methylanthranilate production by engineered Corynebacterium glutamicum. Microorganisms. 2020;8: 866.
Walter, T., Al Medani, N., Burgardt, A., Cankar, K., Ferrer, L., Kerbs, A., Lee, J. - H., et al. (2020). Fermentative N-methylanthranilate production by engineered Corynebacterium glutamicum. Microorganisms, 8, 866. doi:10.3390/microorganisms8060866
Walter, T., Al Medani, N., Burgardt, A., Cankar, K., Ferrer, L., Kerbs, A., Lee, J. - H., Mindt, M., Risse, J. M., and Wendisch, V. F. (2020). Fermentative N-methylanthranilate production by engineered Corynebacterium glutamicum. Microorganisms 8:866.
Walter, T., et al., 2020. Fermentative N-methylanthranilate production by engineered Corynebacterium glutamicum. Microorganisms, 8: 866.
T. Walter, et al., “Fermentative N-methylanthranilate production by engineered Corynebacterium glutamicum”, Microorganisms, vol. 8, 2020, : 866.
Walter, T., Al Medani, N., Burgardt, A., Cankar, K., Ferrer, L., Kerbs, A., Lee, J.-H., Mindt, M., Risse, J.M., Wendisch, V.F.: Fermentative N-methylanthranilate production by engineered Corynebacterium glutamicum. Microorganisms. 8, : 866 (2020).
Walter, Tatjana, Al Medani, Nour, Burgardt, Arthur, Cankar, Katarina, Ferrer, Lenny, Kerbs, Anastasia, Lee, Jin-Ho, Mindt, Melanie, Risse, Joe Max, and Wendisch, Volker F. “Fermentative N-methylanthranilate production by engineered Corynebacterium glutamicum”. Microorganisms 8 (2020): 866.
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2020-06-30T11:21:47Z
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