Biocatalytic Redox Reactions for Organic Synthesis: Nonconventional Regeneration Methods

TLDR

Redox enzymes offer high selectivity and catalytic efficiency under mild conditions, making them attractive for preparative organic synthesis, but their dependence on cofactors remains a major barrier. This work explores unconventional nonenzymatic cofactor regeneration to provide simple, robust reaction schemes that bypass cofactor dependence and deliver redox power directly to enzyme active sites. The authors review three strategies to overcome cofactor limitations: whole‑cell systems, biomimetic enzymatic regeneration, and unconventional nonenzymatic regeneration.

Abstract

Abstract Redox enzymes have tremendous potential as catalysts for preparative organic chemistry. Their usually high selectivity, paired with their catalytic efficiency under mild reaction conditions, makes them potentially very valuable tools for synthesis. The number of interesting monooxygenases, dehydrogenases, reductases, oxidases, and peroxidases is steadily increasing and the tailoring of a given biocatalyst is more and more becoming standard technology. However, their cofactor dependency still represents a major impediment en route to true preparative applicability. Currently, three different approaches to deal with this ‘cofactor challenge’ are being pursued: using whole cells, biomimetic approaches comprising enzymatic cofactor regenerations systems, and ‘unconventional’ nonenzymatic regeneration. The latter technique offers the promise of enabling simple, easily applicable, and robust reaction schemes, for example, by circumventing the ‘cofactor challenge’ and introducing redox power directly to the enzyme’s active sites.