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 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 h with 15 min residence and a constant supply of oxygen for cofactor recycling through a segmented air-liquid flow. The addition of an in-line catch-and-release column afforded >80% product recovery.
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| http://dx.doi.org/10.1039/d1gc01095f | DOI Listing |
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