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ABSTRACT:
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.
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