A Conserved Nonribosomal Peptide Synthetase in Xenorhabdus bovienii Produces Citrulline-Functionalized Lipopeptides
| Autor: | Jhe-Hao Li, Randy Hamchand, Joonseok Oh, Jason M. Crawford, Wooyoung Cho |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Pharmaceutical Science
Article Xenorhabdus Analytical Chemistry Lipopeptides Symbiosis Nonribosomal peptide Drug Discovery medicine Metabolomics Peptide Synthases Gene Pharmacology Comparative genomics chemistry.chemical_classification Molecular Structure biology Effector Chemistry fungi Organic Chemistry Computational Biology biology.organism_classification Protease inhibitor (biology) Complementary and alternative medicine Biochemistry Citrulline Molecular Medicine Heterologous expression Bacteria medicine.drug |
| Zdroj: | J Nat Prod |
| ISSN: | 1520-6025 0163-3864 |
| Popis: | The entomopathogenic bacterium Xenorhabdus bovienii exists in a mutualistic relationship with nematodes of the genus Steinernema. Free-living infective juveniles (IJs) of Steinernema prey on insect larvae and regurgitate X. bovienii within the hemocoel of a host larva. X. bovienii subsequently produces a complex array of specialized metabolites and effector proteins that kill the insect and regulate various aspects of the trilateral symbiosis. While Xenorhabdus species are rich producers of secondary metabolites, many of their biosynthetic gene clusters remain uncharacterized. Here, we describe a nonribosomal peptide synthetase (NRPS) identified through comparative genomics analysis that is widely conserved in Xenorhabdus species. Heterologous expression of this NRPS gene from X. bovienii in E. coli led to the discovery of a family of lipo-tripeptides that chromatographically appear as pairs, containing either a C-terminal carboxylic acid or carboxamide. Co-expression of the NRPS with the leupeptin protease inhibitor pathway enhanced production, facilitating isolation and characterization efforts. The new lipo-tripeptides were also detected in wildtype X. bovienii cultures. These metabolites termed bovienimides share an uncommon C-terminal D-citrulline residue. The NRPS lacked a dedicated chain termination domain resulting in product diversification and release from the assembly line through reactions with ammonia, water, or exogenous alcohols. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|