The transmission of antibiotic-resistance genes, comprising mobilization and relocation events, orchestrates the dissemination of antimicrobial resistance. Inspired by this evolutionarily successful paradigm, we developed ACTIMOT, a CRISPR-Cas9–based approach to unlock the vast chemical diversity concealed within bacterial genomes. ACTIMOT enables the efficient mobilization and relocation of large DNA fragments from the chromosome to replicative plasmids within the same bacterial cell. ACTIMOT circumvents the limitations of traditional molecular cloning methods involving handling and replicating large pieces of genomic DNA. Using ACTIMOT, we mobilized and activated four cryptic biosynthetic gene clusters from Streptomyces , leading to the discovery of 39 compounds across four distinct classes. This work highlights the potential of ACTIMOT for accelerating the exploration of biosynthetic pathways and the discovery of natural products.

中文翻译：

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自体 DNA 动员和增殖可加速从细菌中发现天然产物


抗生素耐药基因的传递，包括动员和重新定位事件，协调了抗菌素耐药性的传播。受这种进化上成功的范式的启发，我们开发了 ACTIMOT，这是一种基于 CRISPR-Cas9 的方法，用于解锁隐藏在细菌基因组中的巨大化学多样性。ACTIMOT 能够有效地动员和重新定位大 DNA 片段从染色体到同一细菌细胞内的复制质粒。ACTIMOT 规避了传统分子克隆方法的局限性，该方法涉及处理和复制大片段基因组 DNA。使用 ACTIMOT，我们从链霉菌中动员并激活了四个隐蔽的生物合成基因簇，从而发现了四个不同类别的 39 种化合物。这项工作突出了 ACTIMOT 在加速探索生物合成途径和发现天然产物方面的潜力。