Fermentative Production of Halogenated Tryptophan Derivatives with Corynebacterium glutamicum Overexpressing Tryptophanase or Decarboxylase Genes

The aromatic amino acid l‐tryptophan serves as a precursor for many valuable compounds such as neuromodulators, indoleamines and indole alkaloids. In this work, tryptophan biosynthesis was extended by halogenation followed by decarboxylation to the respective tryptamines or cleavage to the respective indoles. Either the tryptophanase genes tnaAs from E. coli and Proteus vulgaris or the aromatic amino acid decarboxylase genes AADCs from Bacillus atrophaeus, Clostridium sporogenes, and Ruminococcus gnavus were expressed in Corynebacterium glutamicum strains producing (halogenated) tryptophan. Regarding indoles, final titers of 16 mg L−1 7‐Cl‐indole and 23 mg L−1 7‐Br‐indole were attained. Tryptamine production led to a much higher titer of 2.26 g L−1 upon expression of AADC from B. atrophaeus. AADC enzymes were shown to be active with halogenated tryptophan in vitro and in vivo and supported production of 0.36 g L−1 7‐Br‐tryptamine with a volumetric productivity of 8.3 mg L−1 h−1 in a fed‐batch fermentation. A tryptophan overproducing Corynebacterium glutamicum strain was metabolically engineered to produce 7‐Br/Cl‐indole and 7‐Br/Cl‐tryptamine. For this purpose, tryptophanases and aromatic l‐amino acid decarboxylases from different origins were screened and utilized in combination with halogenase RebH. Fermentative production of 7‐Br‐tryptamine in a bioreactor resulted in a product titer of 0.36 g L−1.