The validamycins were isolated from Streptomyces hygroscopicus var. limoneus and they show pronounced activity against pathogenic fungi. The most abundant representative, validamycin A contains a valienamine moiety linked via a nitrogen bridge to a second cyclitol, validamine, in which the double bond has been reduced; in addition, C-4 of this second cyclitol carries a molecule of glucose in a ß-glycosidic linkage. Other congeners of this family differ from validamycin A in the structure of the second cyclitol moiety or by the presence of additional glucose moieties. Because of its strong inhibitory effect on Rhizoctonia solani, the causative agent of sheath blight disease of rice plants, validamycin A is used extensively in the Far East as a crop protectant. Validamycin A was also the starting point for the development of a second generation alpha-amylase inhibitor, the semi-synthetic compound voglibose (Basen, Takeda Pharmaceutical Co., Ltd.), which is 20 times more potent as an enzyme inhibitor than acarbose and is now also marketed as an anti-diabetic agent. Despite the presence of the valienamine moiety in their structures the validamycins do not inhibit alpha-glycosidases or alpha-amylases; they are, however, potent inhibitors of trehalase. Since trehalose is a major storage saccharide in Rhizoctonia solani, and also a prominent component in the blood of many insects, the inhibition of its breakdown appears to be the mode of action underlying the inhibition of this fungus by validamycin as well as its significant activity against certain insects. In addition to the pseudotrisaccharide and its derivatives, the validamycin fermentation has also yielded a number of simple aminocyclitols, such as valienamine, validamine, and valiolamine.
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