Farnesol dehydrogenase from Helicoverpa armigera (Hübner) as a promising target for pest management: molecular docking, in vitro and insect bioassay studies using geranylgeraniol as potential inhibitor

Rakesh Kumar; Joy Das; Surabhi Rode; Harry Kaur; Vivek Shah; Pooja Verma; Ashwani Kumar Sharma

doi:10.1007/s13205-023-03598-9

Farnesol dehydrogenase from Helicoverpa armigera (Hübner) as a promising target for pest management: molecular docking, in vitro and insect bioassay studies using geranylgeraniol as potential inhibitor

3 Biotech. 2023 Jun;13(6):175. doi: 10.1007/s13205-023-03598-9. Epub 2023 May 11.

Authors

Rakesh Kumar^#^{1

2}, Joy Das^#^{1

2}, Surabhi Rode¹, Harry Kaur¹, Vivek Shah², Pooja Verma², Ashwani Kumar Sharma¹

Affiliations

¹ Department of Biosciences and Bioengineering, Indian Institute of Technology Roorkee, Roorkee, 247667 Uttarakhand India.
² ICAR-Central Institute for Cotton Research, Nagpur, Maharashtra India.

^# Contributed equally.

Abstract

Juvenile hormone (JH) plays pivotal roles in several critical developmental processes in insects, including metamorphosis and reproduction. JH-biosynthetic pathway enzymes are considered highly promising targets for discovering novel insecticides. The oxidation of farnesol to farnesal, catalysed by farnesol dehydrogenase (FDL), represents a rate-limiting step in JH biosynthesis. Here, we report farnesol dehydrogenase (HaFDL) from H. armigera as a promising insecticidal target. The inhibitory potential of natural substrate analogue geranylgeraniol (GGol) was tested in vitro, wherein it showed a high binding affinity (kd 595 µM) for HaFDL in isothermal titration calorimetry (ITC) and subsequently exhibited dose-dependent enzyme inhibition in GC-MS coupled qualitative enzyme inhibition assay. Moreover, the experimentally determined inhibitory activity of GGol was augmented by the in silico molecular docking simulation which showed that GGol formed a stable complex with HaFDL, occupied the active site pocket and interacted with key active site residues (Ser¹⁴⁷ and Tyr¹⁶²) as well as other residues that are crucial in determining the active site architecture. Further, the diet-incorporated oral feeding of GGol caused detrimental effects on larval growth and development, exhibiting a significantly reduced rate of larval weight gain (P < 0.01), aberrant pupal and adult morphogenesis, and a cumulative mortality of ~ 63%. To the best of our knowledge, the study presents the first report on evaluating GGol as a potential inhibitor for HaFDL. Overall, the findings revealed the suitability of HaFDL as a potential insecticidal target for the management H. armigera.

Keywords: Farnesol dehydrogenase; GC–MS; Geranylgeraniol; Helicoverpa armigera; ITC; Juvenile hormone; Molecular docking.

© King Abdulaziz City for Science and Technology 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.