Synergistic Enzyme-Assisted Extraction Strategies for Phenolic Compounds: Integrating Emerging Technologies, Green Solvents, and Process Intensification

Abstract The increasing demand for sustainable and high-value bioactive ingredients has intensified the search for extraction strategies capable of overcoming the structural complexity of plant matrices and improving the recovery of phenolic compounds. In this context, the integration of hydrolytic enzymes with emerging extraction technologies has emerged as a promising approach to enhance extraction efficiency and selectivity. This review critically discusses the synergistic interactions between enzymatic hydrolysis and emerging extraction technologies, including high-intensity ultrasound, microwave-assisted extraction, pressurized liquid extraction, and supercritical fluid extraction. Particular emphasis is placed on the mechanisms by which hydrolytic enzymes disrupt plant cell wall structures and hydrolyze glycosidic bonds, promoting the release of bound phenolics and the formation of more bioactive aglycone derivatives. The effects of process parameters, matrix characteristics, and mass transfer phenomena on extraction performance are also critically examined. In addition, the role of green solvents, especially natural deep eutectic solvents and mixtures based on natural compounds, is explored regarding enzyme activity, extraction efficiency, and process sustainability. Hybrid and sequential extraction configurations are comparatively analyzed to identify technological advantages and operational trade-offs associated with process intensification. Beyond conventional descriptive approaches, this review provides an integrated engineering perspective on enzyme-assisted extraction systems by connecting enzymatic mechanisms, extraction technologies, solvent interactions, and sustainability aspects within a unified process framework. Overall, the findings highlight the potential of intensified enzyme-assisted extraction systems for sustainable valorization of agro-industrial residues into high-value functional ingredients while advancing greener and more efficient bioprocessing strategies.