德国亥姆霍兹感染研究中心Chengzhang Fu和Rolf Müller共同合作，近期取得重要工作进展。他们研究开发了自体DNA调动和繁殖方法，加快了从细菌中发现天然产品的速度。相关研究成果
据介绍，抗生素耐药性基因的传播，包括动员和重新定位事件，协调了抗生素耐药性的传播。
受这一演化成功范式的启发，研究人员开发了ACTIMOT，这是一种基于CRISPR-Cas9的方法，可以解锁细菌基因组中隐藏的巨大化学多样性。ACTIMOT能够有效地将染色体上的大DNA片段动员和重新定位到同一细菌细胞内的复制质粒中。
ACTIMOT规避了传统分子克隆方法的局限性，涉及处理和复制大块基因组DNA。利用ACTIMOT，研究人员从链霉菌中动员并激活了四个神秘的生物合成基因簇，从而发现了四个不同类别的39种化合物。
总之，这一研究突出了ACTIMOT在加速探索生物合成途径和发现天然产物方面的潜力。
附：英文原文
Title: Autologous DNA mobilization and multiplication expedite natural products discovery from bacteria
Author: Feng Xie, Haowen Zhao, Jiaqi Liu, Xiaoli Yang, Markus Neuber, Amay Ajaykumar Agrawal, Amninder Kaur, Jennifer Herrmann, Olga V. Kalinina, Xiaoyi Wei, Rolf Müller, Chengzhang Fu
Issue&Volume: 2024-12-13
Abstract: 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.
DOI: abq7333
Source: https://www.science.org/doi/10.1126/science.abq7333