validoxylamine-a and validamycins

A gene encoding beta-glucosidase was cloned and over-expressed in Escherichia coli. Validamycin A was then biotransformed into validoxylamine A by using the resting recombinant cells. The biotransformation yield reached 92% when the reaction was performed at 37 degrees C for 1 h in the presence of 100 ml sodium phosphate buffer (0.1 M, pH 7.0), 32 mM validamycin A and 0.71 mg dry cell w/ml.

Topics: beta-Glucosidase; Biotransformation; Escherichia coli; Hydrogen-Ion Concentration; Inositol; Temperature

The inhibitory effects of various nitrogen-containing sugars on porcine kidney trehalase were studied. Validamycin A, validoxylamine A and MDL 25,637 were found to be potent, time-dependent inhibitors of the enzyme in vitro. The validoxylamine A-inhibited enzyme showed slow but reversible reactivation over time (t1/2 = 1.2 h). To our knowledge, this is the first report of time-dependent inhibition exhibited by either these particular aminosugars or a trehalase.

Topics: Amino Sugars; Animals; In Vitro Techniques; Inositol; Kidney; Kinetics; Substrate Specificity; Sugar Alcohols; Swine; Trehalase; Trehalose

Validoxylamine A showed a potent inhibitory activity against insect trehalase in a competitive manner with a Ki value of 4.3 x 10(-10) M. The other validoxylamines and validamycins also exhibited the activity in vitro. Injection of these compounds to young last instar larvae of the tobacco cutworm, Spodoptera litura, elicited the morphological abnormality followed by death after the cessation of feeding. Validoxylamine A showed 100% mortality at a dose of 10 micrograms/ last instar larva.

Topics: Animals; Antifungal Agents; Inositol; Insecticides; Lepidoptera; Moths; Trehalase