Broad-Specificity Screening of Pyrethroids Enabled by the Catalytic Function of Human Serum Albumin on Coumarin Hydrolysis

Abstract

Sensing systems based on cholinesterase and carboxylesterase coupled with different transduction technologies have emerged for pesticide screening owing to their simple operation, fast response, and suitability for on-site analysis. However, the broad spectrum and specificity screening of pyrethroids over organophosphates and carbamates remains an unmet challenge for current enzymatic sensors. Human serum albumin (HSA), a multifunctional protein, can promote various chemical transformations and show a high affinity for pyrethroids, which offer a route for specific and broad-spectrum pyrethroid screening. Herein, for the first time, we evaluated the catalytic hydrolysis function of human serum albumin (HSA) on the coumarin lactone bond and revealed that HSA can act as an enzyme to catalyze the hydrolysis of the coumarin lactone bond. Molecular docking and chemical modifications indicate that lysine 199 and tyrosine 411 serve as the catalytic general base and contribute to most of the catalytic activity. Utilizing this enzymatic activity, a broad specific ratiometric fluorescence pyrethroids sensing system was developed. The binding energetics and binding constants of pesticides and HSA show that pyrethroids bind to HSA more easily than organophosphates and carbamates, which is responsible for the specificity of the sensing system. This study provides a general sensor platform and strategy for screening pesticides and reveals the catalytic activity of HSA on the hydrolysis of the coumarin lactone bond, which may open innovative horizons for the chemical sensing and biomedical applications of HSA.

Unveiling the Modification of Esterase-like Activity of Serum Albumin by Nanoplastics and Their Cocontaminants

“…41 HSA-based biosensors have been developed as an application to detect ester-containing substances or to monitor enzymatic processes involving ester substrates. 42 It may also be useful in drug delivery systems, where ester bonds are exploited as cleavable linkers for the regulated release of medicines. 43 Drugs and pollutants may bind nonspecifically or specifically at Sudlow's sites I and II of HSA, potentially influencing its enzymatic function.…”

“…In some clinical circumstances, such as liver disorders, where alterations to HSA structure or binding qualities may affect its enzymatic activity, the esterase activity of HSA may be changed . HSA-based biosensors have been developed as an application to detect ester-containing substances or to monitor enzymatic processes involving ester substrates . It may also be useful in drug delivery systems, where ester bonds are exploited as cleavable linkers for the regulated release of medicines .…”