Ureases in nature: Multifaceted roles and implications for plant and human health - A review

Urease, a multifunctional enzyme that catalyzes the hydrolysis of urea into ammonia, plays a pivotal role in nitrogen metabolism across diverse organisms. While essential for survival, its unregulated activity is implicated in numerous pathologies, including peptic ulcers, nephropathy, and gastric cancer, as well as agricultural challenges such as soil ammonium depletion and reduced nitrogen-use efficiency. Beyond its canonical enzymatic function, urease engages in protein-protein interactions with bioactive counterparts like jaburetox, canatoxin, and soyuretox plant-derived proteins with insecticidal, antifungal, and membranolytic properties. Exploring the relationship between ureases and these proteins, along with their mechanistic synergies, presents novel opportunities to develop targeted inhibitors for urease-related diseases while unlocking broader therapeutic and biotechnological applications. This review delves into the dual roles of ureases in plants and humans, bridging the gap between their ureolytic and non-ureolytic activities. We highlight recent advances in the design of urease inhibitors, which have emerged as critical tools for managing pathologies such as Helicobacter pylori-induced ulcers and urease-mediated kidney stone formation. These inhibitors also hold transformative potential in agriculture, where they mitigate nitrogen loss by stabilizing urea fertilizers, thereby enhancing crop yields and reducing environmental pollution. Furthermore, their utility extends to industrial biotechnology, including biofilm disruption and wastewater treatment, where urease inhibition prevents microbially induced corrosion and ammonia toxicity. The collected information is anticipated to offer insightful guidance and effective strategies for developing novel potent and safe urease inhibitors in the future.