Protease from Streptomyces griseus (SGP) as a sustainable biocatalyst was successfully applied in the Michael/cyclization reaction between dimedone and aryl or alkyl substituted alpha,beta-unsaturated ketones or ester for the synthesis of 3,4-dihydropyran derivatives. The products were obtained in moderate to excellent yields (46-95%) with certain enantioselectivities (up to 18% ee) for 27 examples. This process afforded a potential biocatalytic approach as alternative to chemical synthesis for 3,4-dihydropyran derivatives. Protease from Streptomyces griseus (SGP) was used as a catalyst in the Michael addition/cyclization reaction for the synthesis of 3,4-dihydropyran derivatives. [GRAPHICS] .