Toward the Sustainable Production of the Active Pharmaceutical Ingredient Metaraminol

Metaraminol is an active pharmaceutical ingredient for hypotension treatment and can serve as a precursor for otherbioactive compounds. The production of metaraminol was shownpreviously in an enzymatic cascade consisting of a carboligationand transamination step using the oil-based amine donorisopropylamine. Alternatively, renewableL-alanine can be used.By iterative strain and process engineering, the microbialproduction of pyruvate andL-alanine withCorynebacteriumglutamicumin a one-pot fermentation process was achieved. Thesubsequent biotransformation was realized by direct carboligationof 3-OH-benzaldehyde and biobased pyruvate to (R)-3-OH-phenylacetylcarbinol in the fermentation supernatant with highyields (>= 92% conversion) and stereoselectivity (>98%ee) afteroptimization. The decoupled transamination step utilized biobasedL-alanine for metaraminol synthesis. This study elucidates thecompatibility of biocatalytic conversions in complex fermentation matrices and highlights implications for the integration of novel biobased processes