Toward the Sustainable Production of the Active Pharmaceutical Ingredient Metaraminol

Mohamed Labib, Laura Grabowski, Christian Brüsseler, Nicolai Kallscheuer, Luisa Wachtendonk, Thomas Fuchs, Andreas Jupke, Wolfgang Wiechert, Jan Marienhagen, Dörte Rother, Stephan Noack*

*Korrespondierende/r Autor/-in für diese Arbeit

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.
OriginalspracheEnglisch
ZeitschriftACS Sustainable Chemistry and Engineering
Jahrgang10
Ausgabenummer16
Seiten (von - bis)5117-5128
Seitenumfang12
DOIs
PublikationsstatusVeröffentlicht - 25.04.2022

DFG-Fachsystematik

  • 201-01 Biochemie

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