Better than Nature: Nicotinamide Biomimetics That Outperform Natural Coenzymes

TLDR

Affordable, green biocatalytic processes are sought for chemical manufacturing, yet redox transformations depend on unstable, expensive nicotinamide coenzymes, making stoichiometric use economically unviable and hindering catalytic recycling. The study investigates the efficiency of synthetic biomimetics of NAD(P)H as coenzymes in redox biocatalysis. The authors evaluate these biomimetics with various ene reductases and crystal structure analysis to assess their performance. The biomimetics proved to be excellent analogues of natural coenzymes, outperforming them in selected cases, and are poised for widespread use in fine and specialty chemical production.

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.