Smart cosubstrate
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A smart cosubstrate is a type of cosubstrate used for cofactor regeneration to yield greater productivity and lower environmental impact (E-factor). A good example of a smart cosubstrate is a lactonizable diol.
In redox biocatalysis, the nicotinamide cofactor (NAD(P)H or NAD(P)+) can act as an electron donor or acceptor by releasing or accepting a hydride. The cofactor must be used in the reaction either in stoichiometric amounts leading to inhibition and economic issues, or in catalytic amounts coupled with an in situ regeneration system. A common approach catalytic amounts is excess use of sacrificial organic molecules such as isopropanol or ethanol. This approach, however, leads to stoichiometric amounts of waste.
The use of 1,4-butanediol as a smart cosubstrate for cofactor regeneration was the next step towards more sustainable redox biocatalysis (Scheme 1).[1] The formation of a thermodynamically stable gamma-butyrolactone as a co-product drives the reaction to completion while yielding higher reaction rates. The use of 1,4-butanediol as an intelligent cosubstrate has also been validated in non-aqueous media using a commercial ADH.[2][3]
