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. © 2025 Society of Chemical Industry.