4.6 Article

Toward the Sustainable Production of the Active Pharmaceutical Ingredient Metaraminol

期刊

ACS SUSTAINABLE CHEMISTRY & ENGINEERING
卷 10, 期 16, 页码 5117-5128

出版社

AMER CHEMICAL SOC
DOI: 10.1021/acssuschemeng.1c08275

关键词

amine transaminase; amino alcohol; biocatalysis; pyruvate; Corynebacterium glutamicum; enzyme cascade; L-alanine; metaraminol

资金

  1. Bioeconomy Science Center
  2. Ministry of Innovation, Science and Research within the framework of the NRW Strategieprojekt BioSC [313/323400-002 13]

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This study achieved the microbial production of pyruvate and L-alanine in a one-pot fermentation process, and then transformed them into Metaraminol with high yields and stereoselectivity through a series of reactions.
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

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