The antifungal agent validamycin A is an important crop protectant and the source of valienamine, the precursor of the antidiabetic drug voglibose. Inactivation of the valN gene in the validamycin A producer, Streptomyces hygroscopicus subsp. jinggangensis 5008, resulted in a mutant strain that produces new secondary metabolites 1,1′-bis-valienamine and validienamycin. The chemical structures of 1,1′-bis-valienamine and validienamycin were elucidated by 1D and 2D nuclear magnetic resonance (NMR) spectroscopy in conjunction with mass spectrometry and bioconversion employing a glycosyltransferase enzyme, ValG. 1,1′-Bis-valienamine and validienamycin exhibit a moderate antifungal activity against Pellicularia sasakii. Chemical degradation of 1,1′-bis-valienamine using N-bromosuccinimide followed by purification of the products with ion-exchange column chromatography only resulted in valienamine, whereas parallel treatments of validoxylamine A, the aglycon of validamycin A, resulted in an approximately 1:1 mixture of valienamine and validamine, underscoring the advantage of 1,1′-bis-valienamine over validoxylamine A as a commercial source of valienamine.
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This work was supported by grants from the National Institutes of Health (RO1 AI061528). Work at Shanghai Jiaotong University was supported by grants from the 973 and 863 Programs of the Ministry of Science and Technology, the Natural Science Foundation of China, and Shanghai Leading Academic Discipline Project B203. HX was in part supported by the exchange program from China Scholarship Council.
Hui Xu and Jongtae Yang contributed equally to this paper.
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Xu, H., Yang, J., Bai, L. et al. Genetically engineered production of 1,1′-bis-valienamine and validienamycin in Streptomyces hygroscopicus and their conversion to valienamine. Appl Microbiol Biotechnol 81, 895–902 (2009). https://doi.org/10.1007/s00253-008-1711-z