Issue 12, 2021

Biocatalytic access to betazole using a one-pot multienzymatic system in continuous flow

Abstract

As an alternative to classical synthetic approaches for the production of betazole drug, a one-pot biocatalytic system for this pharmaceutical molecule from its alcohol precursor has been developed. An ω-transaminase, an alcohol dehydrogenase and a water-forming NADH oxidase for in situ cofactor recycling have been combined to catalyse this reaction, yielding 75% molar conversion in batch reactions with soluble enzymes. This multienzyme system was then co-immobilised through a newly established protocol for sequential functionalization of a methacrylate-based porous carrier to enable tailored immobilisation chemistries for each enzyme. This pluri-catalytic system has been set up in a continuous flow packed-bed reactor, generating a space–time yield of up to 2.59 g L−1 h−1 with 15 min residence and a constant supply of oxygen for in situ cofactor recycling through a segmented air–liquid flow. The addition of an in-line catch-and-release column afforded >80% product recovery.

Graphical abstract: Biocatalytic access to betazole using a one-pot multienzymatic system in continuous flow

Supplementary files

Article information

Article type
Paper
Submitted
30 מרץ 2021
Accepted
24 מאי 2021
First published
24 מאי 2021
This article is Open Access
Creative Commons BY-NC license

Green Chem., 2021,23, 4594-4603

Biocatalytic access to betazole using a one-pot multienzymatic system in continuous flow

M. Romero-Fernandez and F. Paradisi, Green Chem., 2021, 23, 4594 DOI: 10.1039/D1GC01095F

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