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Biosynthesis of a Flavonol from a Flavanone by Establishing a One-pot Bienzymatic Cascade
Published on: August 14, 2019
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Biocatalytic access to betazole using a one-pot multienzymatic system in continuous flow
Maria Romero-Fernandez1, Francesca Paradisi1,2
1School of Chemistry, University of Nottingham, University Park NG7 2RD Nottingham UK.
Green Chemistry : an International Journal and Green Chemistry Resource : GC
|July 5, 2021
Summary
A novel one-pot biocatalytic system efficiently produces the betazole drug using immobilized enzymes in a continuous flow reactor. This green chemistry approach offers high conversion and product recovery, advancing pharmaceutical manufacturing.
Area of Science:
- Biocatalysis
- Chemical Engineering
- Pharmaceutical Synthesis
Background:
- Classical synthetic routes for betazole production can be inefficient and environmentally taxing.
- Developing sustainable and efficient methods for pharmaceutical synthesis is crucial.
Purpose of the Study:
- To develop a one-pot biocatalytic system for betazole production from its alcohol precursor.
- To engineer a multi-enzyme system for efficient and continuous synthesis.
Main Methods:
- Combined ω-transaminase, alcohol dehydrogenase, and NADH oxidase for in situ cofactor recycling.
- Co-immobilized enzymes onto a methacrylate-based porous carrier using a novel sequential functionalization protocol.
- Utilized a continuous flow packed-bed reactor with segmented air-liquid flow for oxygen supply.
Main Results:
- Achieved 75% molar conversion in batch reactions with soluble enzymes.
- Generated a space-time yield of up to 2.59 g L-1 h-1 in the continuous flow reactor.
- Implemented an in-line catch-and-release column for >80% product recovery.
Conclusions:
- The developed one-pot, multi-enzyme biocatalytic system is a viable and efficient alternative to traditional betazole synthesis.
- Enzyme immobilization and continuous flow technology enhance catalytic efficiency and product recovery.
- This approach represents a significant advancement in green chemistry for pharmaceutical manufacturing.
