Biocatalytic cofactor recycled efficiently

Oxidoreductase enzymes are used extensively as biocatalysts for industrial and academic reactions, including pharmaceutical synthesis. But they almost exclusively require expensive cofactors such as NADP⁺, the oxidized form of the biological cofactor nicotinamide adenine dinucleotide phosphate. The reagent currently costs about $22,000 per mole. Enzymes that can recycle it from its reduced form, NADPH, have drawbacks that have limited their use, such as low activity, unwanted by-product generation, and short lifetimes. Guided by nature, which uses an NADP⁺-producing glutathione reductase system to maintain a reducing environment within cells, researchers have now developed a similar system for regenerating NADP⁺ from NADPH. Rudolf K. Allemann of Cardiff University and coworkers devised the system, which uses an organic-disulfide oxidizing agent and bacterial glutaredoxin and glutathione reductase to regenerate NADP⁺ (ACS Catal. 2016, DOI: 10.1021/acscatal.6b03061). The primary recurrent cost is for the inexpensive organic disulfides, so the process could reduce the price of NADP⁺ to about $0.05 per mole, a more than five-order-of-magnitude improvement. The system, which “is superior to all existing methods” for regenerating NADP⁺, “offers many advantages for commercial and academic users,” the researchers say.