A novel short‐chain dehydrogenase/reductase catalyzing efficient patulin detoxification: identification and computational characterization

BACKGROUND Patulin (PAT), a widespread mycotoxin produced by Aspergillus and Penicillium genera, commonly contaminates fruits, vegetables and their derived products. Due to its water solubility, PAT poses significant health risks through food‐chain accumulation. RESULTS In this study, a novel short‐chain dehydrogenase/reductase (SDR) from Lachancea mirantina (LmSDR) is reported, which achieves complete PAT degradation under pH 6.0 and 50 °C. LmSDR retains high activity across a pH range of 5.0–6.5. In the presence of NADPH, LmSDR exhibits excellent substrate tolerance, degrading over 70% of PAT even at high concentrations (50 μg mL −1 ). Furthermore, LmSDR demonstrates considerable thermal stability, maintaining more than 85% residual activity after a 1 h incubation at 40 °C, with a melting temperature of 44 °C. Using AI‐assisted structural modeling and molecular docking, three pivotal residues, Tyr156, Ser140 and His185, were identified as critical for NADPH‐mediated proton transfer, facilitating PAT reduction to less toxic ( E )‐ascladiol. Moreover, in silico mutagenesis pinpointed several residues essential for LmSDR‐mediated PAT degradation, thereby providing a theoretical basis for the rational engineering of LmSDR and other PAT‐degrading SDRs. CONCLUSION The acidic pH preference of LmSDR indicates its optimal activity under mildly acidic conditions, highlighting its potential as a biocatalyst for applications in acidic food matrices. Moreover, computer‐aided approaches offer a theoretical framework for elucidating the proton transfer mechanism of LmSDR and other PAT‐degrading SDRs.