Insect-Associated Bacteria Assemble the Antifungal Butenolide Gladiofungin by Non-Canonical Polyketide Chain Termination
Open Access
- 14 December 2020
- journal article
- research article
- Published by Wiley in Angewandte Chemie-International Edition
- Vol. 59 (51), 23122-23126
- https://doi.org/10.1002/anie.202005711
Abstract
Genome mining of one of the protective symbionts (Burkholderia gladioli) of the invasive beetleLagria villosarevealed a cryptic gene cluster that codes for the biosynthesis of a novel antifungal polyketide with a glutarimide pharmacophore. Targeted gene inactivation, metabolic profiling, and bioassays led to the discovery of the gladiofungins as previously-overlooked components of the antimicrobial armory of the beetle symbiont, which are highly active against the entomopathogenic fungusPurpureocillium lilacinum. By mutational analyses, isotope labeling, and computational analyses of the modular polyketide synthase, we found that the rare butenolide moiety of gladiofungins derives from an unprecedented polyketide chain termination reaction involving a glycerol-derived C3 building block. The key role of an A-factor synthase (AfsA)-like offloading domain was corroborated by CRISPR-Cas-mediated gene editing, which facilitated precise excision within a PKS domain.Funding Information
- Deutsche Forschungsgemeinschaft (SFB 1127/2 - 239748522, Leibniz Award, DFG FL1051/1-1, KA2846/2-2, KA2846/6-1)
This publication has 45 references indexed in Scilit:
- Chemical Ecology of Endophytic Fungi: Origins of Secondary MetabolitesCell Chemical Biology, 2012
- The Butenolide Signaling Molecules SRB1 and SRB2 Induce Lankacidin and Lankamycin Production in Streptomyces rocheiChemBioChem, 2012
- Bacterial symbionts and natural productsChemical Communications, 2011
- Multifaceted Modes of Action for the Glutarimide‐Containing Polyketides RevealedChemBioChem, 2010
- Functionally Distinct Modules Operate Two Consecutive α,β→β,γ Double‐Bond Shifts in the Rhizoxin Polyketide Assembly LineAngewandte Chemie, 2010
- Functionally Distinct Modules Operate Two Consecutive α,β→β,γ Double‐Bond Shifts in the Rhizoxin Polyketide Assembly LineAngewandte Chemie, 2010
- In vitro reconstruction of tetronate RK-682 biosynthesisNature Chemical Biology, 2009
- iso-Migrastatin, Migrastatin, and Dorrigocin Production in Streptomyces platensis NRRL 18993 Is Governed by a Single Biosynthetic Machinery Featuring an Acyltransferase-less Type I Polyketide SynthaseOnline Journal of Public Health Informatics, 2009
- Analysis of the Tetronomycin Gene Cluster: Insights into the Biosynthesis of a Polyether Tetronate AntibioticChemBioChem, 2008
- Biosynthesis of γ-butyrolactone autoregulators that switch on secondary metabolism and morphological development in StreptomycesProceedings of the National Academy of Sciences of the United States of America, 2007