More efficient redox biocatalysis by utilising 1,4-butanediol as a ‘smart cosubstrate’

Abstract

is shown to be an efficient cosubstrate to promote NAD(P)H-dependent redox biocatalysis. The thermodynamically and kinetically inert lactone coproduct makes the regeneration reaction irreversible. Thereby not only the molar surplus of cosubstrate is dramatically reduced but also faster reaction rates are obtained. Scheme 1 Comparison of the 'classical' biocatalytic MPV-reduction e.g. using isopropanol and the proposed 'smart cosubstrate' approach using 1,4-butanediol. The lactone coproduct renders the regeneration reaction irreversible. The lower part shows the equilibrium conversions as calculated from the law of mass action (lines) and the waste generated (bars). † Electronic supplementary information (ESI) available: Detailed description of the experimental and analytical procedures and further experimental data. See

Recent advances in whole cell biocatalysis techniques bridging from investigative to industrial scale

“…Because of the high affinity of the catalyst to organic media/substrates, 97% of the model substrate 2,2,2-trifluoroacetophenon could be converted within 48 h to a remarkable product concentration of 634 g L À1 [28]. The concept of neat substrate systems was further adapted to the stereoselective production of (R)-and (S)-2-butanol 'Smart' diol cosubstrates are oxidized twice thus generating two equivalents of regenerated cofactor before lactone formation [17]. [29 ].…”

“…Of course, such approaches rely on proper balancing of reaction rates of both enzymatic reactions and on the effectiveness and efficiency of such a route to access the product of interest. Another novel strategy is the use of 'smart' diol cosubstrates ( Figure 1) [17]. After double oxidation of the diol, a stable lactone ring is formed, which drives the thermodynamic equilibrium to the product side.…”

Enzymatic Oxyfunctionalization Driven by Photosynthetic Water-Splitting in the Cyanobacterium Synechocystis sp. PCC 6803

“…Several alternative solutions for this challenge are currently under consideration. Coupling oxidative and reductive steps to redox-neutral enzyme cascades [3] is a very promising approach, and it allows for potential savings also in whole-cell biotransformations. However, this is not applicable for reactions without neutral redox balance or with decoupling, i.e., the need of an excess of redox cofactor.…”

Nicotinamide Adenine Dinucleotide‐Dependent Redox‐Neutral Convergent Cascade for Lactonizations with Type II Flavin‐Containing Monooxygenase

“…[13] Remarkably, HLADH has been used to promote redox biocatalysis using 1,4-butanediol as a "smart cosubstrate", as the thermodynamically stable and kinetically inert coproduct lactone makes the regeneration reaction irreversible. [14] It is worth mentioning here that 1,4-butanediol can be obtained from renewable feedstocks at commercial scale which has been developed by Genomatica Inc. (San Diego, USA) [15] and their fermentative synthesis process has been recently licensed by BASF SE (Germany). HLADHa well-known ADH for diol oxidation -was chosen to perform the convergent cascade with FMOÀE.…”