Upgraded Bioelectrocatalytic N₂ Fixation: From N₂ to Chiral Amine Intermediates

Area of Science:

• Biocatalysis
• Bioelectrocatalysis
• Organic Synthesis

Background:

• Chiral amines are crucial building blocks for pharmaceuticals and agrochemicals.
• Enantioselective synthesis of chiral amines often faces equilibrium limitations.
• ω-Transaminase (ω-TA) offers high enantioselectivity and broad substrate scope for amination reactions.

Purpose of the Study:

• To develop an upgraded nitrogen (N₂) fixation system for efficient chiral amine production.
• To overcome equilibrium limitations in ω-TA catalyzed reactions using bioelectrocatalysis.
• To enable the direct conversion of N₂ into valuable chiral amine intermediates.

Main Methods:

• Integration of a bioelectrocatalytic N₂ fixation system with ω-TA and l-alanine dehydrogenase.
• In situ ammonia production and conversion to alanine using NADH regeneration.
• Electrochemical regeneration of reduced methyl viologen (MV•+) and NADH at the cathode.
• Utilizing pyruvate consumption to drive the reaction equilibrium towards amine formation.

Main Results:

• Successful conversion of N₂ to chiral amine intermediates with high enantiomeric excess (>99% eeₚ).
• Achieved a concentration of 0.54 mM 1-methyl-3-phenylpropylamine after 10 hours.
• Demonstrated a maximum faradaic efficiency of 27.6% for the process.
• Showcased the synchronous regeneration of MV•+ and NADH via cathodic reduction.

Conclusions:

• The developed bioelectrocatalytic system effectively overcomes equilibrium limitations in chiral amine synthesis.
• This approach provides a sustainable pathway for producing diverse chiral amine intermediates from N₂.
• The system holds significant potential for pharmaceutical and agrochemical applications due to ω-TA's versatility.