Department of Chemistry, University of Montana, Missoula, MT 59812, USA.
Bioorg Med Chem Lett. 2010 Oct 1;20(19):5936-8. doi: 10.1016/j.bmcl.2010.06.146. Epub 2010 Jul 7.
We have shown that the intentional engineering of a natural product biosynthesis pathway is a useful way to generate stereochemically complex scaffolds for use in the generation of combinatorial libraries that capture the structural features of both natural products and synthetic compounds. Analysis of a prototype library based upon nonactic acid lead to the discovery of triazole-containing nonactic acid analogs, a new structural class of antibiotic that exhibits bactericidal activity against drug resistant, Gram-positive pathogens including Staphylococcus aureus and Enterococcus faecalis.
我们已经证明，有目的地设计天然产物生物合成途径是一种生成用于组合文库的立体化学复杂支架的有用方法，这些文库可以捕捉天然产物和合成化合物的结构特征。基于壬酸的原型文库的分析导致了含有三唑的壬酸类似物的发现，这是一类新的抗生素结构，对包括金黄色葡萄球菌和粪肠球菌在内的耐药革兰阳性病原体具有杀菌活性。
