Discovery and Biosynthesis of Azabicyclene, a Conserved Nonribosomal Peptide in Pseudomonas aeruginosa.
Jon B PattesonAdam R LescalletteBo LiPublished in: Organic letters (2019)
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.
Keyphrases
- pseudomonas aeruginosa
- genome wide identification
- transcription factor
- genome wide
- cystic fibrosis
- cell wall
- copy number
- biofilm formation
- endothelial cells
- poor prognosis
- acinetobacter baumannii
- small molecule
- genome wide analysis
- dna methylation
- candida albicans
- induced pluripotent stem cells
- single cell
- escherichia coli
- binding protein
- case control
- pluripotent stem cells
- staphylococcus aureus