A Redox–Lipid Transcriptional State Is Associated with High Aflatoxin Biosynthetic Activity in Aspergillus flavus

Background/Objectives: Aflatoxin B1 (AFB1) contamination of maize and peanut is influenced by fungal responses to environmental and food-matrix cues, but the transcriptional coordination of redox adaptation, lipid metabolism, and aflatoxin biosynthesis remains unresolved. This study examined whether an expression-defined redox–lipid state is associated with high relative aflatoxin biosynthetic activity in Aspergillus flavus. Methods: A cross-dataset secondary analysis integrated 18 analytical datasets (247 samples) derived from eight public source records spanning defined-medium, maize, and peanut systems. Harmonized expression profiles were used to derive an aflatoxin biosynthetic activity score (ABAS), oxidative-stress adaptation score (OSAS), and lipid metabolic reprogramming score (LMRS). ABAS is an expression-derived relative score, not a direct measure of biosynthetic flux or accumulated toxin. Dataset-aware mixed-effects models evaluated the OSAS–ABAS association and the linear OSAS × LMRS interaction. Results: ABAS correlated with matched AFB1 measurements in 54 samples (Pearson r=0.734, p=2.70×10−10). The quadratic OSAS term was negative (β=−0.434, 95% CI −0.502 to −0.366; p<0.001), with maximum predicted ABAS near 0.81 SD on the pooled within-dataset-standardized OSAS scale. Separately, the linear OSAS × LMRS interaction was positive (β=0.284, 95% CI 0.198–0.370; p<0.001), and the high-OSAS/high-LMRS quadrant had the greatest adjusted mean ABAS (0.789, 95% CI 0.661–0.917). Candidate prioritization recovered established regulators and nominated redox- and lipid-associated nodes. Conclusions: The findings identify an associative transcriptional signature across heterogeneous food-relevant conditions and provide focused hypotheses for prospective validation using direct toxin, redox, lipid, flux, and functional measurements.