H₂-driven cofactor regeneration with NAD(P)⁺-reducing hydrogenases

Area of Science:

• Biocatalysis
• Enzyme Engineering
• Sustainable Chemistry

Background:

• Nicotinamide cofactors are essential for many industrial enzymes but are prohibitively expensive for stoichiometric use.
• Current NAD(P)H-recycling systems often exhibit low activity or produce unwanted byproducts.
• Sustainable and cost-effective cofactor regeneration is critical for the economic viability of enzymatic processes.

Purpose of the Study:

• To review the advancements in hydrogen (H₂)-driven cofactor regeneration systems.
• To explore the integration of these systems with enzymatic reactions.
• To evaluate the potential of specific enzymes, like Ralstonia eutropha hydrogenase, for technical applications.

Main Methods:

• Literature review of H₂-driven cofactor regeneration technologies.
• Analysis of enzyme integration with cofactor regeneration systems.
• Detailed examination of the catalytic properties of O₂-tolerant NAD⁺-reducing hydrogenase from Ralstonia eutropha.

Main Results:

• H₂-driven cofactor regeneration offers 100% atom efficiency and utilizes a cheap, sustainable reducing agent.
• Several H₂-driven systems have been developed and integrated with various enzyme-catalyzed reactions.
• The O₂-tolerant hydrogenase from Ralstonia eutropha demonstrates significant promise for industrial cofactor regeneration.

Conclusions:

• H₂-driven cofactor regeneration presents a highly efficient and sustainable alternative to existing methods.
• The O₂-tolerant hydrogenase from Ralstonia eutropha is a key candidate for robust and scalable biocatalytic processes.
• Further development of H₂-driven systems can significantly reduce the cost of enzymatic synthesis.