Genetically engineered production of 1,1'-bis-valienamine and validienamycin in Streptomyces hygroscopicus and their conversion to valienamine.
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.
Xu
Hui
H
Department of Pharmaceutical Sciences, Oregon State University, 203 Pharmacy Building, Corvallis, OR 97331, USA.
Yang
Jongtae
J
Bai
Linquan
L
Deng
Zixin
Z
Mahmud
Taifo
T
D000935:Antifungal Agents / Q000378:metabolism / Q000494:pharmacology; D053138:Cyclohexenes / Q000494:pharmacology; D005658:Fungi / Q000187:drug effects; D017353:Gene Deletion; D005798:Genes, Bacterial; D006595:Hexosamines / Q000096:biosynthesis* / Q000494:pharmacology; D007294:Inositol / Q000031:analogs & derivatives / Q000096:biosynthesis; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D013302:Streptomyces / Q000235:genetics* / Q000378:metabolism*
D000935:Antifungal Agents; D053138:Cyclohexenes; D006595:Hexosamines; C030791:valienamine; D007294:Inositol; C003749:validamycins