Toward the Sustainable Production of the Active Pharmaceutical Ingredient Metaraminol

Abstract

Metaraminol is an active pharmaceutical ingredient for hypotension treatment and can serve as a precursor for other bioactive compounds. The production of metaraminol was shown previously in an enzymatic cascade consisting of a carboligation and transamination step using the oil-based amine donor isopropylamine. Alternatively, renewable l-alanine can be used. By iterative strain and process engineering, the microbial production of pyruvate and l-alanine with Corynebacterium glutamicum in a one-pot fermentation process was achieved. The subsequent biotransformation was realized by direct carboligation of 3-OH-benzaldehyde and biobased pyruvate to (R)-3-OH-phenylacetylcarbinol in the fermentation supernatant with high yields (≥92% conversion) and stereoselectivity (>98% ee) after optimization. The decoupled transamination step utilized biobased l-alanine for metaraminol synthesis. This study elucidates the compatibility of biocatalytic conversions in complex fermentation matrices and highlights implications for the integration of novel biobased processes.