Smart cosubstrate

A common approach catalytic amounts is excess use of sacrificial organic molecules such as isopropanol or ethanol.

The use of 1,4-butanediol as a smart cosubstrate for cofactor regeneration was the next step towards more sustainable redox biocatalysis (Scheme 1).

[6][7][8] The concept of a smart cosubstrate was developed further through the design of a new class of redox-neutral "convergent cascade" reactions.

Convergent cascade reactions involve a bi-substrate and a single product without the formation of an intermediate and were developed for the production of epsilon-caprolactone, which consists of a Baeyer-Villiger monooxygenase; for the oxidation of cyclohexanone; an alcohol dehydrogenase for oxidation of the "double-smart cosubstrate" 1,6-hexanediol; and for simultaneous regeneration of the nicotinamide cofactor.

[10] Smart cosubstrates are an elegant solution for thermodynamically limited redox reactions and have many advantages:

Comparison of the use of isopropanol (left) to the "smart cosubstrate" approach using 1,4-butanediol . The lactone coproduct makes the regeneration reaction irreversible
Synthesis of ɛ-caprolactone (ECL) through a convergent cascade system by coupling a Baeyer–Villiger monooxygenase (BVMO)-catalyzed oxidation of cyclohexanone (CHO) to ECL, promoted by an alcohol dehydrogenase (ADH)-catalyzed oxidation of the ‘double-smart cosubstrate’ 1,6-hexanediol (1,6-HD) for regeneration of NAD(P)H , yielding ECL.