Application of epoxide hydrolases in synthesizing chiral drug compounds has been hindered by their limited substrate range and low stereoselectivity.The enzymatic production of bulky epoxides has proven remarkably challenging.In this talk, I will mainly present three work: 1.Identification of an active tunnel for substrate access and product release in an epoxide hydrolase with unusual (R)-enantioselectivity.2.Engineering the smart library of epoxide hydrolase for efficient bioresolution of bulky pharmaco substrates.3.The structural basis of epoxide hydrolases with enhanced and inverted stereoselectivity.