Department of Chemical and Biological Engineering, Princeton University, Princeton, New Jersey 08544, United States.
Laboratory of Molecular Biophysics and Tri-Institutional Training Program in Chemical Biology, Rockefeller University, New York, New York 10065, United States.
J Nat Prod. 2023 Nov 24;86(11):2448-2456. doi: 10.1021/acs.jnatprod.3c00536. Epub 2023 Oct 23.
Through genome mining efforts, two lasso peptide biosynthetic gene clusters (BGCs) within two different species of , a genus that contains pathogenic organisms that can infect patients with cystic fibrosis, were discovered. Using gene-refactored BGCs in , these lasso peptides, which were named achromonodin-1 and achromonodin-2, were heterologously expressed. Achromonodin-1 is naturally encoded by certain isolates from the sputum of patients with cystic fibrosis. The NMR structure of achromonodin-1 was determined, demonstrating that it is a threaded lasso peptide with a large loop and short tail structure, reminiscent of previously characterized lasso peptides that inhibit RNA polymerase (RNAP). Achromonodin-1 inhibits RNAP and has potent, focused activity toward , another isolate from the sputum of a cystic fibrosis patient. These efforts expand the repertoire of antimicrobial lasso peptides and provide insights into how isolates from certain ecological niches interact with each other.
通过基因组挖掘工作，在两种不同的 物种中发现了两个拉索肽生物合成基因簇（BGCs），该属包含可感染囊性纤维化患者的致病性生物体。使用 中的基因重构 BGCs，这些拉索肽被命名为 achromonodin-1 和 achromonodin-2，并进行了异源表达。achromonodin-1 是由囊性纤维化患者痰中某些分离株天然编码的。achromonodin-1 的 NMR 结构已被确定，表明它是一种带有大环和短尾结构的穿线拉索肽，类似于先前表征的抑制 RNA 聚合酶（RNAP）的拉索肽。achromonodin-1 抑制 RNAP ，对 具有强烈的、集中的活性，这是另一种从囊性纤维化患者痰中分离出来的菌株。这些努力扩展了抗菌拉索肽的 repertoire ，并深入了解了某些生态位的 分离株如何相互作用。
