Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
J Nat Prod. 2024 Jul 26;87(7):1694-1703. doi: 10.1021/acs.jnatprod.3c01231. Epub 2024 Jul 1.
Combination therapy is an effective strategy to combat antibiotic resistance. Multiple synergistic antimicrobial combinations are produced by enzymes encoded in biosynthetic gene clusters (BGCs) that co-localize on the bacterial genome. This phenomenon led to the hypothesis that mining co-localized BGCs will reveal new synergistic combinations of natural products. Here, we bioinformatically identified 38 pairs of co-localized BGCs, which we predict to produce natural products that are related to known compounds, including polycyclic tetramate macrolactams (PoTeMs). We further showed that ikarugamycin, a PoTeM, increases the membrane permeability of and , which suggests that ikarugamycin might be an adjuvant that facilitates the entry of other natural products. Our work outlines a promising avenue to discover synergistic combinations of natural products by mining bacterial genomes.
联合治疗是对抗抗生素耐药性的有效策略。生物合成基因簇（BGCs）编码的酶在细菌基因组上共定位，产生多种协同抗菌组合。这一现象导致了这样一种假设，即挖掘共定位 BGC 将揭示天然产物的新协同组合。在这里，我们通过生物信息学方法鉴定了 38 对共定位 BGC，我们预测这些 BGC 将产生与已知化合物相关的天然产物，包括多环四肽大环内酯（PoTeMs）。我们进一步表明，PoTeM 伊卡鲁霉素增加了 和 的膜通透性，这表明伊卡鲁霉素可能是一种佐剂，有助于其他天然产物的进入。我们的工作为通过挖掘细菌基因组来发现天然产物协同组合的方法提供了一个很有前途的途径。
