Department of Chemistry , University of North Carolina at Chapel Hill CB 3290, Chapel Hill , North Carolina 27599-3290 , United States.
Org Lett. 2019 Jul 5;21(13):4955-4959. doi: 10.1021/acs.orglett.9b01383. Epub 2019 Jun 25.
Azabicyclene, an azetidine-containing natural product, was identified using quorum-sensing molecules to upregulate expression of a gene cluster highly conserved in the human pathogen Pseudomonas aeruginosa. Mutational studies of the gene cluster revealed essential genes for biosynthesis, including an unusual nonribosomal peptide synthetase. Reconstitution of this enzyme in vitro identified key biosynthetic intermediates. This work demonstrates a useful strategy for discovering quorum-sensing-regulated natural products. It sets the stage for understanding the biosynthesis and bioactivity of azabicyclene.
氮杂双环[3.1.0]己烷，一种含有氮杂环丁烷的天然产物，使用群体感应分子鉴定，以上调在人类病原体铜绿假单胞菌中高度保守的基因簇的表达。对基因簇的突变研究揭示了生物合成的必需基因，包括一种不寻常的非核糖体肽合成酶。该酶在体外的重建鉴定了关键的生物合成中间体。这项工作证明了一种发现群体感应调节天然产物的有用策略。它为理解氮杂双环[3.1.0]己烷的生物合成和生物活性奠定了基础。
