Bacterial Alkaloid Biosynthesis: Structural Diversity via a Minimalistic Nonribosomal Peptide Synthetase

Cell Chem Biol. 2018 Jun 21;25(6):659-665.e9. doi: 10.1016/j.chembiol.2018.02.013. Epub 2018 Mar 29.

Abstract

Chemical and biochemical analyses of one of the most basic nonribosomal peptide synthetases (NRPS) from a Pseudomonas fluorescens strain revealed its striking plasticity. Determination of the potential substrate scope enabled us to anticipate novel secondary metabolites that could subsequently be isolated and tested for their bioactivities. Detailed analyses of the monomodular pyreudione synthetase showed that the biosynthesis of the bacterial pyreudione alkaloids does not require additional biosynthetic enzymes. Heterologous expression of a similar and functional, yet cryptic, NRPS of Pseudomonas entomophila was successful and allowed us to perform a phylogenetic analysis of their thioesterase domains.

Keywords: A domain specificity; Dieckmann cyclization; Pseudomonas; Te domain phylogeny; bacterial alkaloids; biosynthesis; heterologous expression; monomodular nonribosomal peptide synthetase; pyreudiones.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / biosynthesis*
  • Alkaloids / chemistry
  • Dictyostelium / chemistry
  • Dictyostelium / metabolism
  • Escherichia coli / chemistry
  • Escherichia coli / metabolism*
  • Molecular Structure
  • Peptide Synthases / metabolism*
  • Pseudomonas / chemistry
  • Pseudomonas / metabolism*

Substances

  • Alkaloids
  • Peptide Synthases
  • non-ribosomal peptide synthase