State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
Metab Eng. 2011 May;13(3):336-44. doi: 10.1016/j.ymben.2011.01.002. Epub 2011 Feb 1.
Acting as competitive inhibitors of chitin synthase, nikkomycins and polyoxins are potent antibiotics against pathogenic fungi. Taking advantage of the structural similarities between these two peptidyl nucleoside antibiotics, genes required for the biosynthesis of the dipeptidyl moiety of polyoxin from Streptomyces cacaoi were introduced into a Streptomyces ansochromogenes mutant producing the nucleoside moiety of nikkomycin X. Two hybrid antibiotics were generated. One of them was identified as polyoxin N, and the other, a novel compound, was named polynik A. The hybrid antibiotics exhibited merits from both parents: they had better inhibitory activity against phytopathogenic fungi than polyoxin B, and were more stable under different pH and temperature conditions than nikkomycin X. This study demonstrates the use of the combinatorial biosynthetic approach to produce valuable and novel hybrid antibiotics with improved properties.
作为几丁质合成酶的竞争性抑制剂， nikkomycins 和 polyoxins 是针对致病真菌的强效抗生素。利用这两种肽基核苷抗生素之间的结构相似性，将产生可可链霉菌中环二肽部分所需的基因引入产生 nikkomycin X 核苷部分的变铅青链霉菌突变体中。产生了两种混合抗生素。其中一种被鉴定为 polyoxin N，另一种是新化合物，命名为 polynik A。这些混合抗生素具有双亲的优点：它们对植物病原真菌的抑制活性优于 polyoxin B，并且在不同的 pH 值和温度条件下比 nikkomycin X 更稳定。这项研究证明了组合生物合成方法的应用，可以生产出具有改良特性的有价值的新型混合抗生素。
