Farnesol dehydrogenase from Metisa plana (Lepidoptera: Psychidae): Biochemical characterization, in silico analysis and inhibitors discovery.

Metisa plana (Lepidoptera: Psychidae), a foliar-feeding bagworm, is a major pest in oil palm plantations, particularly in Peninsular Malaysia. Government of Malaysia has classified it as a dangerous pest under the Plant Quarantine Act 1976. Effective and sustainable solutions remain elusive despite various management strategies, including chemical, cultural and biological methods. This study explored an alternative approach by targeting the juvenile hormone biosynthetic pathway, crucial for insect growth, metamorphosis, and reproduction, as part of the Integrated Pest Management (IPM) strategy. Specifically, the rate-limiting enzyme farnesol dehydrogenase from M. plana (MpFolDH) was expressed, purified and biochemically characterized. MpFolDH, a heterodimeric enzyme comprising of 255 amino acids with a molecular weight of 54 kDa, exhibited high substrate specificity for trans, trans-farnesol, utilizing NADP+ as its sole coenzyme. It functioned optimally at 35 °C and pH 9. The predicted structural analysis using AlphaFold3, molecular docking and molecular dynamics simulation revealed stable interactions, with MM/PBSA binding free energy of -64.61 ± 0.80 kJ/mol. Other than that, ZINC000408735138, previously identified through virtual screening, was tested alongside three farnesol analogs in an in-vitro inhibition assay. ZINC000408735138 exhibited the most potent inhibition (3.94 ± 0.342 μM), with Ki value approximately 35 times lower than the other tested farnesol analog, indicating competitive inhibition. In contrast, farnesyl acetate demonstrated a promising uncompetitive inhibition mode. This study provides critical biochemical insights into MpFolDH as a potential insecticide target and identifies promising inhibitors, offering a foundation for novel strategies to combat M. plana infestation.