Palaniappan Nadaraj, Dhote Vidya, Ayers Sloan, Starosta Agata L, Wilson Daniel N, Reynolds Kevin A
Department of Chemistry, Portland State University, OR 97207-0751, USA.
Chem Biol. 2009 Nov 25;16(11):1180-9. doi: 10.1016/j.chembiol.2009.10.013.
The 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 Deltahyg6 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.
潮霉素A（HA）的抗菌活性源于对蛋白质合成的抑制作用，且依赖于一个亚甲二氧基桥连的氨基环醇部分。在吸水链霉菌NRRL 2388中进行的选择性基因缺失和化学互补实验表明，推测可生成肌醇中间体的hyg18和hyg25基因产物对于HA的生物合成并非必需，但对抗生素产量有贡献。推测可引入胺官能团的Hyg8和Hyg17对于HA的生物合成至关重要。Hyg6是一种作用于氨基环醇的甲基转移酶，hyg6缺失突变体产生去甲亚基潮霉素A。hyg7是一个金属依赖性水解酶同源基因，其缺失导致甲氧基潮霉素A的产生，这表明相应的基因产物负责推测的亚甲二氧基桥形成的氧化环化步骤。甲基/亚甲基对于体外蛋白质合成抑制并非必需，但对于抗大肠杆菌活性至关重要。
