TY  - JOUR
AB  - 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.
DA  - 2020
DO  - 10.3390/microorganisms8060866
KW  - N-functionalized amines
KW  - N-methylanthranilate
KW  - Corynebacterium glutamicum
KW  - metabolic engineering
KW  - sustainable production of quinoline precursors
KW  - acridone
KW  - quinazoline alkaloid drugs
LA  - eng
PY  - 2020
T2  - Microorganisms
TI  - Fermentative N-methylanthranilate production by engineered Corynebacterium glutamicum
UR  - https://nbn-resolving.org/urn:nbn:de:0070-pub-29437553
Y2  - 2024-11-22T01:57:20
ER  -