Mesh : Aspergillus fumigatus / metabolism genetics Piperazines / chemistry metabolism Gliotoxin / biosynthesis chemistry Molecular Structure Chaetomium / metabolism chemistry CRISPR-Cas Systems

来  源:   DOI:10.1021/acs.orglett.4c01274

Abstract:
Using CRISPR-Cas9 technology and a microhomology-mediated end-joining repair system, we substituted genes of the gliotoxin pathway in Aspergillus fumigatus with genes responsible for chetomin biosynthesis from Chaetomium cochliodes, leading to the production of three new epipolythiodioxopiperazines (ETPs). This work represents the first successful endeavor to produce ETPs in a non-native host. Additionally, the simultaneous disruption of five genes in a single transformation marks the most extensive gene knockout event in filamentous fungi to date.
摘要:
使用CRISPR-Cas9技术和微同源介导的末端连接修复系统,我们将烟曲霉胶质毒素途径的基因替换为负责从耳蜗毛霉生物合成切托明的基因,导致生产三种新的表聚硫代二氧哌嗪(ETP)。这项工作代表了在非本地主机中产生ETP的第一个成功尝试。此外,在一次转化中同时破坏5个基因标志着迄今丝状真菌中最广泛的基因敲除事件。
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