Entropy-driven Denaturation for Sustainable Regeneration of Protein Waste.

Electrolytes are essential parts of the environment for all life forms, where proteins, water, and solutes interplay to support vital activities. However, a fundamental understanding of the effect of ionic solutes on proteins remains elusive for more than a century. Here we show how some ionic solutes can serve as potent denaturants despite the absence of direct protein-ion interactions. We demonstrate dramatic differences between denaturation potency of different ionic solutes with lithium bromide (LiBr) being the strongest denaturant and sodium bromide (NaBr) being the least potent. Experiments and simulations indicate the presence of certain ions disrupts the structure of water network, thereby induce protein denaturation indirectly via an entropy-driven mechanism. We further introduce a scalable strategy for protein waste revalorization, distinguished by the closed-loop recycling of denaturants, straightforward protein separation, and facile manufacturing, all enabled by the entropy-driven denaturation by LiBr. Through successful isolation and systematic study of indirect solute effects, our findings suggest a unified and generally applicable framework for decoding of the protein-water-solute nexus, where all current studies can be easily incorporated. Besides, our regeneration approach underscores the feasibility of repurposing protein waste into valuable biomaterials in a sustainable way with wide-reaching application potential.