Bridging Biosynthesis and Bioavailability: Integrated Strategies for Tailoring Soybean Isoflavone Profiles

ABSTRACT Soybean isoflavones (SIs) are pivotal bioactive targets in the growing plant‐based functional food market due to their selective estrogen receptor modulator (SERM)‐like properties. However, a significant disparity remains between agricultural SI accumulation and ultimate physiological efficacy, constrained by the yield‐metabolism genetic antagonism “linkage drag” and the “dual‐cage” matrix entrapment barrier. This review establishes an operationalized seed‐to‐table framework to bridge these gaps through precise profile tailoring. We critically evaluate upstream genetic interventions (e.g., CRISPR/Cas9‐mediated flux redirection) and downstream processing (e.g., biotransformation, physical‐field intensification, and green solvent engineering). A novel, evidence‐based key performance indicator (KPI) matrix is introduced to benchmark these technologies against standardized technology readiness levels (TRLs), economic burden (CapEx/OpEx), and systemic trade‐offs. Crucially, we reframe SI bioavailability by accounting for Phase II metabolism, emphasizing that aglycone enrichment optimizes pharmacokinetic consistency and absorption kinetics rather than absolute systemic exposure. By integrating human clinical evidence and safety considerations for vulnerable populations (e.g., ER+ breast cancer survivors), this work bridges the persistent validation gap between laboratory innovation and clinical outcomes. Finally, we outline a paradigm shift toward AI‐driven digital twins and host metabotyping to resolve the sensory‐bioactivity paradox, providing a scientific roadmap for the rational design of next‐generation isoflavone‐fortified soy foods.