Azetidine‐Containing Alkaloids Produced by a Quorum‐Sensing Regulated Nonribosomal Peptide Synthetase Pathway in Pseudomonas aeruginosa

作者：Zhilai Hong; Arnaud Bolard; Caroline Giraud; Sébastien Prévost; Grégory Genta‐Jouve; Christiane Deregnaucourt; Susanne Häussler; Katy Jeannot; Yanyan Li

来源：Angewandte Chemie, 2019, 131(10): 3210-3214.

DOI：10.1002/ange.201809981

• Alkaloide
• Biosynthese
• Enzyme
• Naturstoffe
• Quorum-Sensing

Abstract Pseudomonas aeruginosa displays an impressive metabolic versatility, which ensures its survival in diverse environments. Reported herein is the identification of rare azetidine‐containing alkaloids from P. aeruginosa PAO1, termed azetidomonamides, which are derived from a conserved, quorum‐sensing regulated nonribosomal peptide synthetase (NRPS) pathway. Biosynthesis of the azetidine motif has been elucidated by gene inactivation, feeding experiments, and biochemical characterization in vitro, which involves a new S‐adenosylmethionine‐dependent enzyme to produce azetidine 2‐carboxylic acid as an unusual building block of NRPS. The mutants of P. aeruginosa unable to produce azetidomonamides had an advantage in growth at high cell density in vitro and displayed rapid virulence in Galleria mellonella model, inferring functional roles of azetidomonamides in the host adaptation. This work opens the avenue to study the biological functions of azetidomonamides and related compounds in pathogenic and environmental bacteria. Das opportunistische Humanpathogen Pseudomonas aeruginosa produziert Azetidin‐2‐carbonsäure, ein Prolin‐Mimetikum, das in das durch Quorum‐Sensing gesteuerte NRPS‐Fließband (NRPS=nichtribosomale Peptidsynthase) eingegliedert wird, wodurch eingeschränkte bicyclische Alkaloide entstehen. Diese Verbindungen haben wichtige Funktionen in der Physiologie von P. aeruginosa.

• 单位
  常州工学院