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Biomimetic Agents for Replacement of NAD+/NADH in Enzymatic Reactions




  • Preparation of chiral, pharmaceuticals, or specialty organic compounds
  • Biosensor technology for medical, chemical and biological sensing


  • Co-factors are stable in air and water
  • Co-factors are designed without sugar, phosphate, or adenine groups
  • Co-factors can be used with a system that prevents co-factor loss downstream
  • The technology enables cost-effective co-factor regeneration

Synthetic co-factors enhance enzymatic catalysis of chiral intermediates

Scheme for operation of a biomimetic membrane system that connects electrodes to the enzyme biocatalyst. The traditional NAD+/NADH co-factors are replaced with inexpensive nicotinamide derivatives, tethered to the the swellable polymer membrane. Optional redox carriers (O & R) are also incorporated to provide necessary regioselectivity in the regeneration process. The system may be driven in either direction to provide a platform for catalysis or sensing and is particularly well-suited for computer controlled processes.


Richard H. Fish, John B. Kerr, and H. Christine Lo have developed several biomimetic NAD+ compounds that enable the production of cost-effective, high value co-factors. These new co-factors will find application in all enzymatic, biocatalysis, and industrial processes that depend on NAD+/1,4-NADH as co-factors for preparation of chiral, pharmaceuticals, or specialty organic compounds.

Between 30-35% of all known enzymes are oxido-reductases and require the use of co-factors to provide sources of reductants and oxidants for the enzymatic reaction to occur. In many cases, the co-factors are NAD+, NADP+, 1,4-NADH or 1,4-NAPDH. The least expensive of these, NAD+, costs ~$2,000/kg, making the co-factors usually much more expensive than the products of the enzymatic reaction.

Berkeley Lab’s new NAD+ compounds fill three distinct requirements for viable synthetic co-factors. (1) They can be regenerated into the desired redox form. (2) They are designed without the natural NAD+ functionalities: the sugar, phosphate, or adenine groups. These are the groups that are typically subject to acid-base hydrolysis reactions that have been reported to lead to inactivity of the co-factors, thus accounting for most of their expense. (3) They can be used with an easily separable support or membrane that provides a suitable means of separation and prevents co-factor loss in downstream processing. This solves one of the major problems currently restricting the use of co-factor regeneration.

Biosensor technology for medical, chemical and biological sensing will be a strong, initial application. With further development, the co-factors potentially could be used in large-scale processing of food, biomass, environmental remediation, and production of renewable feedstocks of chemicals and fuels.

STATUS: U.S. Patent #6,716,596. Available for licensing.





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