Polyphenol Oxidase Inhibition for Browning Control in Fruit and Vegetable Products: Molecular Mechanisms, Computational Screening, and Natural Inhibitors

Enzymatic browning, primarily catalyzed by polyphenol oxidase (PPO), is a major cause of postharvest losses and quality degradation in fresh-cut fruit and vegetable processing. To control this browning, conventional methods such as sulfite treatment and thermal inactivation have been widely used, yet they increasingly face safety, sensory, and regulatory concerns. Because of this, more attention has been directed toward natural PPO inhibitors from agro-industrial by-products as safer, value-added alternatives. However, current knowledge of PPO inhibition mechanisms and rational inhibitor discovery remains fragmented across the literature, limiting the development of effective and sustainable anti-browning approaches. To address this gap, this review presents an integrated framework that covers (i) the structural and kinetic basis of PPO catalysis at the binuclear copper active site; (ii) the mechanistic classification of reversible and irreversible inhibitors, together with kinetic characterization using IC50, Ki, and nonlinear regression approaches; (iii) computational screening strategies, including molecular docking and molecular dynamics simulations as modern tools for predicting enzyme–inhibitor interactions and prioritizing candidate inhibitors; and (iv) the potential of agro-industrial by-products as renewable sources of natural PPO inhibitors for extending the shelf life of fresh-cut produce. Through this framework, this review provides an integrated perspective to support the rational evaluation and future development of effective, sustainable PPO inhibitors for food processing.