Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1391607 | Chemistry & Biology | 2009 | 10 Pages |
SummaryThe antibacterial activity of hygromycin A (HA) arises from protein synthesis inhibition and is dependent upon a methylenedioxy bridged-aminocyclitol moiety. Selective gene deletions and chemical complementation in Streptomyces hygroscopicus NRRL 2388 showed that the hyg18 and hyg25 gene products, proposed to generate a myo-inositol intermediate, are dispensable for HA biosynthesis but contribute to antibiotic yields. Hyg8 and Hyg17, proposed to introduce the amine functionality, are essential for HA biosynthesis. Hyg6 is a methyltransferase acting on the aminocyclitol, and a Δhyg6 mutant produces desmethylenehygromycin A. Deletion of hyg7, a metallo-dependant hydrolase homolog gene, resulted in methoxyhygromycin A production, demonstrating that the corresponding gene product is responsible for the proposed oxidative cyclization step of methylenedioxy bridge formation. The methyl/methylene group is not required for in vitro protein synthesis inhibition but is essential for activity against Escherichia coli.