Unexpected Bacterial Origin of the Antibiotic Icosalide: Two-Tailed Depsipeptide Assembly in Multifarious Burkholderia Symbionts

ACS Chemical Biology
Benjamin DoseChristian Hertweck

Abstract

Icosalide is an unusual two-tailed lipocyclopeptide antibiotic that was originally isolated from a fungal culture. Yet, its biosynthesis and ecological function have remained enigmatic. By genome mining and metabolic profiling of a bacterial endosymbiont ( Burkholderia gladioli) of the pest beetle Lagria villosa, we unveiled a bacterial origin of icosalide. Functional analysis of the biosynthetic gene locus revealed an unprecedented nonribosomal peptide synthetase (NRPS) that incorporates two β-hydroxy acids by means of two starter condensation domains in different modules. This unusual assembly line, which may inspire new synthetic biology approaches, is widespread among many symbiotic Burkholderia species from diverse habitats. Biological assays showed that icosalide is active against entomopathogenic bacteria, thus adding to the chemical armory protecting beetle offspring. By creating a null mutant, we found that icosalide is a swarming inhibitor, which may play a role in symbiotic interactions and bears the potential for therapeutic applications.

References

Jun 13, 2002·Proceedings of the National Academy of Sciences of the United States of America·Tin-Wein YuHeinz G Floss
Oct 17, 2002·Proceedings of the National Academy of Sciences of the United States of America·Jörn Piel
Aug 16, 2003·Environmental Microbiology·Tom Coenye, Peter Vandamme
Oct 7, 2005·Nature·Laila P Partida-Martinez, Christian Hertweck
Aug 31, 2006·Journal of the American Chemical Society·Kirstin ScherlachChristian Hertweck
Nov 24, 2006·Applied and Environmental Microbiology·Laila P Partida-MartinezChristian Hertweck
May 18, 2007·BMC Evolutionary Biology·Christian RauschDaniel H Huson
Nov 6, 2007·International Journal of Systematic and Evolutionary Microbiology·Laila P Partida-MartinezChristian Hertweck
Apr 22, 2008·FEMS Microbiology Reviews·Stéphane CompantEssaïd Ait Barka
Feb 26, 2009·Natural Product Reports·Jörn Piel
Oct 6, 2009·Trends in Microbiology·Gerald LacknerChristian Hertweck
Apr 24, 2010·FEMS Microbiology Reviews·Jos M RaaijmakersMarc Ongena
May 4, 2010·Applied and Environmental Microbiology·Michele T Hoffman, A Elizabeth Arnold
Aug 10, 2010·Nature Reviews. Microbiology·Daniel B Kearns
May 12, 2011·Nucleic Acids Research·Marc RöttigOliver Kohlbacher
Aug 24, 2012·Angewandte Chemie·Kirstin ScherlachChristian Hertweck
Dec 6, 2014·Journal of Natural Products·Souvik KusariMichael Spiteller
Apr 17, 2016·Nucleic Acids Research·Jana TrifinopoulosBui Quang Minh
Jul 29, 2017·Environmental Microbiology·Laura V Flórez, Martin Kaltenpoth
Nov 24, 2017·Current Opinion in Microbiology·Evelyn M Molloy, Christian Hertweck
Apr 19, 2018·ACS Chemical Biology·Tawatchai ThongkongkaewChristian Hertweck

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Citations

Nov 27, 2018·Natural Product Reports·Robert A Hill, Andrew Sutherland
Jul 4, 2019·Chemistry : a European Journal·Sina Rütschlin, Thomas Böttcher
Feb 14, 2020·Organic & Biomolecular Chemistry·Sebastian Götze, Pierre Stallforth
Jul 15, 2020·Annual Review of Microbiology·Kirstin Scherlach, Christian Hertweck
Jun 28, 2019·Frontiers in Microbiology·Philipp HeiseAndreas Vilcinskas
Oct 9, 2019·Annual Review of Entomology·Martin Kaltenpoth, Laura V Flórez
Dec 6, 2019·Frontiers in Microbiology·Aabir BanerjiScott Keely
Jan 21, 2021·Expert Opinion on Drug Discovery·Adam FoxfireLeif Smith
Feb 13, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Hanna ChenHaibo Zhou
Jul 8, 2021·Chembiochem : a European Journal of Chemical Biology·Benjamin DoseChristian Hertweck
Jul 12, 2019·Journal of Natural Products·Sylvia Kunakom, Alessandra S Eustáquio
Aug 19, 2020·ACS Chemical Biology·Aya YoshimuraMohammad R Seyedsayamdost
Dec 4, 2021·ACS Chemical Biology·Brett C Covington, Mohammad R Seyedsayamdost
Oct 5, 2021·Annual Review of Entomology·Hassan Salem, Martin Kaltenpoth

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