Development of Continuous Flow Systems to Access Secondary Amines Through Previously Incompatible Biocatalytic...

Area of Science:

• Biocatalysis and synthetic chemistry
• Enzyme engineering and cascade reactions

Background:

• Eukaryotic cells perform complex, multi-step biochemical reactions efficiently.
• Traditional batch processing limits the complexity and scalability of biocatalytic cascades.
• Developing continuous flow systems is crucial for advanced biocatalysis.

Purpose of the Study:

• To develop continuous flow systems for complex biocatalytic cascades.
• To overcome limitations of batch processing in multi-step enzymatic reactions.
• To demonstrate the synthesis of valuable amine compounds and natural products.

Main Methods:

• Utilized continuous flow reactors to manage reactive intermediates.
• Employed alcohol oxidases for in situ generation of carbonyl compounds.
• Integrated packed-bed modules with various aminating biocatalysts (transaminases, imine reductases).
• Developed a sequential amination cascade using an oxidase/transaminase/imine reductase system.

Main Results:

• Successfully generated reactive carbonyl intermediates in situ.
• Produced a range of structurally distinct amines using packed-bed biocatalyst modules.
• Achieved a batch-incompatible sequential amination cascade without cross-reactivity.
• Synthesized the natural product 4O-methylnorbelladine via a multi-step flow biocatalysis approach.

Conclusions:

• Continuous flow systems are effective for complex biocatalytic cascades.
• This methodology enables the synthesis of amines and complex natural products.
• The developed system overcomes batch incompatibility issues in enzymatic synthesis.