Biocatalytic Thiophosphorylation Achieved With ATPγS Recycling

Researchers have developed a novel strategy for recycling Adenosine 5'-[γ-thio]triphosphate (ATPγS), a critical component for biocatalytic thiophosphorylation, as reported in Nature on July 15, 2026. This breakthrough addresses a significant limitation in utilizing ATPγS, which is often consumed irreversibly in enzymatic reactions, making large-scale applications economically unfeasible.

The new method employs a coupled enzymatic system that regenerates ATPγS from its byproduct, Adenosine 5'-[γ-thio]diphosphate (ADPγS). This recycling process allows for the continuous use of ATPγS, drastically reducing the amount of the expensive reagent required for thiophosphorylation reactions. The researchers demonstrated the efficacy of this strategy by successfully performing biocatalytic thiophosphorylation of various substrates, including proteins and small molecules, with high yields and specificity.

Thiophosphorylation is a crucial chemical modification that introduces a sulfur atom into a molecule, a process vital for the synthesis of numerous pharmaceuticals, agrochemicals, and materials. However, traditional chemical methods for thiophosphorylation can be harsh and lack selectivity. Biocatalysis, using enzymes, offers a milder and more precise alternative, but the high cost of ATPγS has historically hindered its widespread adoption.

The developed recycling system is designed to be compatible with a range of enzymatic thiophosphorylation reactions. By enabling the practical and cost-effective use of ATPγS, this innovation opens new avenues for the development of sulfur-containing compounds through biocatalytic routes. The research team anticipates that this strategy will accelerate the discovery and production of novel molecules with important industrial and therapeutic applications.