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Discovery and Biosynthesis of Azabicyclene, a Conserved Nonribosomal Peptide in Pseudomonas aeruginosa.

ABSTRACT: 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.

SUBMITTER: Patteson JB

PROVIDER: S-EPMC7179086 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Discovery and Biosynthesis of Azabicyclene, a Conserved Nonribosomal Peptide in Pseudomonas aeruginosa.

Patteson Jon B JB Lescallette Adam R AR Li Bo B

Organic letters 20190625 13

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-reg ...[more]

PMID: 31247735

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