还原型烟酰胺腺嘌呤二核苷酸磷酸(NADPH)是代谢网络中的关键辅因子。NADPH的有效再生是生物转化过程中生产率的限制因素之一。迄今为止,已经开发了许多代谢工程工具和静态调节策略来调节NADPH再生。然而,传统的静态调节方法往往导致NADPH/NADP+失衡,导致细胞生长和生产中断。这些方法也不能提供细胞内NADP(H)或NADPH/NADP+水平的实时监测。近年来,已经开发了各种生物传感器用于检测,监测,动态调节细胞内NADP(H)水平或NADPH/NADP+平衡。这些与NADPH相关的生物传感器主要用于细菌的辅因子工程,酵母,和哺乳动物细胞。本文从静态和动态两个角度分析和总结了NADPH代谢调控策略,强调当前的挑战和潜在的解决方案,并讨论了NADPH/NADP+平衡高级调节的未来方向。
Reduced nicotinamide adenine dinucleotide phosphate (NADPH) is a crucial cofactor in metabolic networks. The efficient regeneration of NADPH is one of the limiting factors for productivity in biotransformation processes. To date, many metabolic engineering tools and static regulation strategies have been developed to regulate NADPH regeneration. However, traditional static regulation methods often lead to the NADPH/
NADP+ imbalance, causing disruptions in cell growth and production. These methods also fail to provide real-time monitoring of intracellular
NADP(H) or NADPH/
NADP+ levels. In recent years, various biosensors have been developed for the detection, monitoring, and dynamic regulate of the intracellular
NADP(H) levels or the NADPH/
NADP+ balance. These NADPH-related biosensors are mainly used in the cofactor engineering of bacteria, yeast, and mammalian cells. This review analyzes and summarizes the NADPH metabolic regulation strategies from both static and dynamic perspectives, highlighting current challenges and potential solutions, and discusses future directions for the advanced regulation of the NADPH/
NADP+ balance.