Sustainable production of the drug precursor tyramine by engineered Corynebacterium glutamicum.

Tyramine has attracted considerable interest due to recent findings that it is an excellent starting material for the production of high-performance thermoplastics and hydrogels. Furthermore, tyramine is a precursor of a diversity of pharmaceutically relevant compounds, contributing to its growing importance. Given the limitations of chemical synthesis, including lack of selectivity and laborious processes with harsh conditions, the biosynthesis of tyramine by decarboxylation of L-tyrosine represents a promising sustainable alternative. In this study, the de novo production of tyramine from simple nitrogen and sustainable carbon sources was successfully established by metabolic engineering of the L-tyrosine overproducing Corynebacterium glutamicum strain AROM3. A phylogenetic analysis of aromatic-L-amino acid decarboxylases (AADCs) revealed potential candidate enzymes for the decarboxylation of tyramine. The heterologous overexpression of the respective AADC genes resulted in successful tyramine production, with the highest tyramine titer of 1.9 g L obtained for AROM3 overexpressing the tyrosine decarboxylase gene of Levilactobacillus brevis. Further metabolic engineering of this tyramine-producing strain enabled tyramine production from the alternative carbon sources ribose and xylose. Additionally, up-scaling of tyramine production from xylose to a 1.5 L bioreactor batch fermentation was demonstrated to be stable, highlighting the potential for sustainable tyramine production. KEY POINTS: • Phylogenetic analysis revealed candidate l-tyrosine decarboxylases • C. glutamicum was engineered for de novo production of tyramine • Tyramine production from alternative carbon substrates was enabled.