Abstract
Squalene hopene cyclases catalyse the conversion of a linear substrate squalene to a cyclic product with high stereo-selectivity.The enzyme squalene hopene cyclase from Pseudomonas mendocina expressed in E. coli BL21 (DE3) was evaluated for its synthetic drug transforming ability. Nine synthetic drugs were selected as substrates for biotransformation reactions by the enzyme. The homology modelling of the protein and docking of the selected ligands were performed using GOLD suite docking software. The drug which showed maximum binding with the active-site residues of the enzyme was selected for biotransformation studies. On transformation with the enzyme, Glibenclamide, the selected antidiabetic drug alone showed significant changes in the FT/IR spectra; hence, it was selected for LCMS analysis to confirm the transformations. From the chromatogram and MS spectra, the mono-oxygenation of the product due to the enzymatic activity was confirmed. The drug transforming ability of the purified SHC could be used as an ideal tool for the generation of new and active substrate derivatives.
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Acknowledgements
We are thankful to Dr.Amjesh Ambu, Junior Scientist Department of Computational Biology and Bioinformatics, University of Kerala for the docking studies of the enzyme and SIIC, University of Kerala for the LCMS analysis
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The author IMN has contributed to the execution of the work and the preparation of the manuscript. The corresponding author KJ contributed to the planning of the work and correction of the manuscript.
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Nair, I.M., Jayachandran, K. In Vitro Enzymatic Conversion of Glibenclamide Using Squalene Hopene Cyclase from Pseudomonas mendocina Expressed in E. coli BL21 (DE3). Mol Biotechnol 62, 456–465 (2020). https://doi.org/10.1007/s12033-020-00264-w
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DOI: https://doi.org/10.1007/s12033-020-00264-w