The industrial production of diosgenin in China generates a large amount of high-sugar wastes with low bioavailability, which causes serious pollution to the environment. In this study, a new clean and efficient process for the production of diosgenin was developed using sugars through in situ high-valued transformation. The sugar mixture from Dioscorea zingiberensis C.H. Wright contained abundant beneficial components. Nine typical microorganisms that produced intracellular products were evaluated. Saccharopolyspora spinosa was selected for recursive protoplast fusion to increase the spinosad yield by 46.3% compared with that of the wildtype. Diosgenin and spinosad co-production was conducted in a 100 L bioreactor, with pH controlled by adding glucose. The biological oxygen demand of the effluent water decreased from 15,000 mg/L to 450 mg/L; hence, the proposed process is environment friendly. (C) 2015 Elsevier Ltd. All rights reserved.