Biocatalytic access to betazole using a one-pot multienzymatic system in continuous flow. Issue 12 (11th June 2021)

• Record Type: Journal Article
• Authors: Romero-Fernandez, Maria; Paradisi, Francesca
• Is Part Of: Green chemistry. Volume 23:Issue 12(2021)
• Page Start: 4594
• Page End: 4603
• Publication Date: 2021-06-11
• Subjects: Environmental chemistry -- Industrial applications -- Periodicals; Environmental management -- Periodicals; 660
• DOI: 10.1039/d1gc01095f
• Languages: English
• ISSNs: 1463-9262

Abstract

Abstract : The primary amine of betazole is synthesised from an alcohol in a one-pot, continuous flow biocatalytic cascade, using a PBR hosting a multienzyme co-immobilised system with constant O2 supply for in situ cofactor recycling, yielding 2.59 g L −1 h −1 . 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.