Abstract
The search for affordable, green biocatalytic processes is a challenge for chemicals manufacture. Redox biotransformations are potentially attractive, but they rely on unstable and expensive nicotinamide coenzymes that have prevented their widespread exploitation. Stoichiometric use of natural coenzymes is not viable economically, and the instability of these molecules hinders catalytic processes that employ coenzyme recycling. Here, we investigate the efficiency of man-made synthetic biomimetics of the natural coenzymes NAD(P)H in redox biocatalysis. Extensive studies with a range of oxidoreductases belonging to the “ene” reductase family show that these biomimetics are excellent analogues of the natural coenzymes, revealed also in crystal structures of the ene reductase XenA with selected biomimetics. In selected cases, these biomimetics outperform the natural coenzymes. “Better-than-Nature” biomimetics should find widespread application in fine and specialty chemicals production by harnessing the power of high stereo-, regio-, and chemoselective redox biocatalysts and enabling reactions under mild conditions at low cost.
Highlights
Through the process of natural selection, Nature has evolved well-adapted macromolecular structures that interact with biological small molecules
We set out to determine the structures of selected complexes formed between Ene reductases (ERs) biocatalysts and the biomimetics to ascertain if the biomimetic design features replicate those seen for the natural enzyme−coenzyme complexes
Each of the three bound biomimetics occupies the same region of the active site as that observed for NADPH4 (Figure 2), with only very minimal changes observed in the positions of surrounding residues in the active site
Summary
Through the process of natural selection, Nature has evolved well-adapted macromolecular structures that interact with biological small molecules. Well as α,β-unsaturated diacids are reduced by ERs.[18] In contrast, the efficient reduction of α,β-unsaturated monoacids or monoesters requires an additional electron-withdrawing group in the α- or β-position in order to activate the alkene moiety.[19−22] The ability to form new stereogenic centers and the wide acceptance of different substrate types are driving the exploitation of ERs toward novel applications in redox biocatalysis and implementation in key industrial processes.[22−25] ERs have been studied extensively over the past decade, and there is detailed information known, such as their structure, reaction mechanism, substrate scope, kinetic properties, and biocatalytic approaches.[26,27,13] The catalytic cycle of ER-catalyzed reactions can be divided into two separated halfreactions: in the reductive half-reaction, a hydride is transferred from NAD(P)H to the enzyme-bound flavin (flavin mononucleotide; FMN). ERs (and mutatis mutandis other redox biocatalysts) under mild reaction conditions and at relatively low cost
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