Multi-omics integration identifies GmISO5 as a key regulator of seed isoflavone biosynthesis and implicates it in the response to soybean mosaic virus

INTRODUCTION: Isoflavones are specialized metabolites that accumulate abundantly in soybean seeds, contributing to nutritional quality, human health benefits, and plant defense. Although the core isoflavone biosynthetic pathway has been well characterized, its upstream regulatory network and potential relationship with plant stress responses remain incompletely understood. OBJECTIVES: This study aimed to identify key regulators of seed isoflavone accumulation and to assess whether the identified regulator is associated with the soybean response to soybean mosaic virus (SMV) infection. METHODS: We integrated genome-wide and transcriptome-wide association analyses with CRISPR/Cas9-mediated knockout, transcriptome profiling, molecular interaction assays, co-expression network analysis, and population genetic analysis. RESULTS: rather than direct selection for reduced isoflavone accumulation. CONCLUSION: GmISO5 is a key regulator of soybean seed isoflavone accumulation that directly activates GmHIDH and GmCHS1. The increased SMV susceptibility of GmISO5 knockout lines further implicates GmISO5 in the soybean response to SMV infection, although whether reduced isoflavone accumulation directly causes the altered SMV phenotype remains to be established.