Production Of Enzyme Inhibitors By Microbial Transformation Of Validamycins

Validamycins have been one of the most popular and economical biopesticides in China, by microbial transformation of which validoxylamine A and valienamine can be produced. Validoxylamine A has strong inhibition on trehalase and it is a new promising insecticide. Valienamine demonstrates strong glucosidase inhibitory activity, which can also be used as intermediate in the synthesis of medicines for diabetes.Firstly the optimal operation conditions for the production of validoxylamine A and degradation of validamycin A were obtained. Our work also found the glucosidase responsible for transformation of validamycin A to validoxylamine A exsited in the fermentation liquor of 24h. The kinetic models about biomass growth, substrate consumption and product accumulatoin were also obtained, and the simulated results agreed well with the experimental data.In the research of production of valienamine by microbial transformation, a possible pathway of degradation of validamycin A was guessed. Then seven methods were tried, which showed that proper content of sulfate or glucose in seed culture medium could improve the production of valienamine greatly.After comparing six methods of embedment of cells, we chose calcium alginate(CA) and K-carrageenan(CGN) to immobilize the cells. When CA-immobilized cells were used, an average of 8.6 g/L valienamine concentration was obtained if concentration of validamycins could be increased up to 120 g/L. Activity of the immobilized cells was increased distinctly through a treatment of the immobilized cells with 0.2 g/L Tween80 or 0.3 mol/L substrate. Compared with free cells, the productivity of valienamine by growing CA-immobilized cells was improved about three times. The diffusion effect was not significant in the immobilized systems from that the value of effectiveness factor was 0.74 and Tiele modulus was 2.70, inferring the degradation process was governed by intraparticle diffusion and chemical reaction.