A retrievable nanostructure heterogeneous catalyst, based on lipase (lipase from the fungus Aspergillus niger), namely Fe3O4-bonded lipase (Fe3O4 NPs@ lipase) was prepared in nano size and fully characterized by several techniques such as Fourier transform infrared spectroscopy, X-ray diffraction, Scanning electron microscopy, Transmission electron microscopy and Vibrating sample magnetometer. The retrievable nanostructure catalyst was asserted to be an efficient catalyst in the synthesis of benzothiazepine and spirobenzothiazine chroman derivatives through three-component reaction of coumarine-3-carboxylic acid derivatives, 2-aminothiophenol, and alkyl isocyanides at room temperature under mild conditions. .