α-Glucosidase Inhibitor--Research And Development Of Valienamine And Its Analogues

valienamine and its related pseudo-sugars demonstrate strong glucosidase inhibitory activity. Its derivatives, acarbose and voglibose which exhibit stronger activities, have been clinically used on antidiabetic treatment. valienamine and its anologues can be obtained by transformation of validamycin A. The research result are as follows: A macroporous strongly acid cation exchange resin HD-8 was selected out for its exchange strength of validamycin A. It was found that the better exchange capacity of resin HD-8 was 167.3mg.ml-1resin. The concentration of validamycin A was 82.5% through resin D261 and NA membrane filtration. The ultimate purity is 99.18% after resin HZ201 purification and its recovery rate is 95.7%. Through research on resting-cell of HCCB 20049, we found that valienamine and validamine can be gained after separation and purification of transformant. A optimum process was obtained after studying on seed age,transformation system,temperature,dissolved oxygen,substrate concentration and resting-cell concentration, which yield is 87.64%. β-glucosidase and 3-dehydrogenase of HCCB 20049-2 are induced by sugar. After studying the relationship within inducing factors,enzyme activities and transformation rate, it was found that when cellobiose was used as inducer, enzyme activities and transformation rate were both higher than other sugars. And the best concentration of cellobiose was 10g/L. According to the reported gene sequence of Halomonas sp.α-15, a fragment was cloned from HCCB 20049 chromosome based on PCR method. The comparison of sequences revealed that the homology between the cloned fragment and Halomonas sp.α-15 was 70.1%.