Ruccolo Serge, Brito Gilmar, Christensen Melodie, Itoh Tetsuji, Mattern Keith, Stone Kevin, Strotman Neil A, Sun Alexandra C
Process Research and Development, Merck & Company Incorporated, Rahway, New Jersey 07065, United States.
J Am Chem Soc. 2022 Dec 14;144(49):22582-22588. doi: 10.1021/jacs.2c08955. Epub 2022 Nov 30.
Adenosine triphosphate (ATP) provides the driving force necessary for critical biological functions in all living organisms. In synthetic biocatalytic reactions, this cofactor is recycled using high-energy stoichiometric reagents, an approach that generates waste and poses challenges with enzyme stability. On the other hand, an electrochemical recycling system would use electrons as a convenient source of energy. We report a method that uses electricity to turn over enzymes for ATP generation in a simplified cellular respiration mimic. The method is simple, robust, and scalable, as well as broadly applicable to complex enzymatic processes including a four-enzyme biocatalytic cascade in the synthesis of the antiviral molnupiravir.
三磷酸腺苷(ATP)为所有生物体内关键的生物功能提供必要的驱动力。在合成生物催化反应中,这种辅因子通过使用高能化学计量试剂进行循环利用,这种方法会产生废物并对酶的稳定性构成挑战。另一方面,电化学循环系统将使用电子作为便捷的能量来源。我们报告了一种方法,该方法利用电力在简化的细胞呼吸模拟中使酶周转以生成ATP。该方法简单、稳健且可扩展,并且广泛适用于复杂的酶促过程,包括抗病毒药物莫努匹拉韦合成中的四酶生物催化级联反应。