Insect-Associated Bacteria Assemble the Antifungal Butenolide Gladiofungin by Non-Canonical Polyketide Chain Termination.
antifungal compounds
biosynthesis
genome mining
natural products
polyketides
Journal
Angewandte Chemie (International ed. in English)
ISSN: 1521-3773
Titre abrégé: Angew Chem Int Ed Engl
Pays: Germany
ID NLM: 0370543
Informations de publication
Date de publication:
14 12 2020
14 12 2020
Historique:
received:
20
04
2020
revised:
10
06
2020
pubmed:
27
6
2020
medline:
23
3
2021
entrez:
27
6
2020
Statut:
ppublish
Résumé
Genome mining of one of the protective symbionts (Burkholderia gladioli) of the invasive beetle Lagria villosa revealed 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 fungus Purpureocillium 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.
Identifiants
pubmed: 32588959
doi: 10.1002/anie.202005711
pmc: PMC7756420
doi:
Substances chimiques
Antifungal Agents
0
Polyketides
0
butenolide
8KXK25H388
4-Butyrolactone
OL659KIY4X
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
23122-23126Informations de copyright
© 2020 The Authors. Published by Wiley-VCH GmbH.
Références
Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4255-E4263
pubmed: 29666226
Org Lett. 2007 Dec 6;9(25):5183-6
pubmed: 17997563
Org Lett. 2013 Mar 15;15(6):1278-81
pubmed: 23438151
Appl Microbiol Biotechnol. 2014 Jun;98(11):4919-36
pubmed: 24562179
Chem Commun (Camb). 2011 Jul 21;47(27):7559-66
pubmed: 21594283
Angew Chem Int Ed Engl. 2020 Dec 14;59(51):23145-23153
pubmed: 32918852
Nature. 2013 Oct 3;502(7469):124-8
pubmed: 24048471
Biochemistry. 2014 Dec 16;53(49):7854-65
pubmed: 25405956
Chembiochem. 2010 Sep 24;11(14):1951-4
pubmed: 20806307
Curr Med Chem. 2006;13(1):39-50
pubmed: 16457638
Nat Prod Rep. 2018 Apr 25;35(4):357-378
pubmed: 29441375
Antimicrob Agents Chemother. 1976 Jul;10(1):14-9
pubmed: 984746
Angew Chem Int Ed Engl. 2020 Mar 27;59(14):5656-5659
pubmed: 31868273
Chembiochem. 2013 May 10;14(7):851-61
pubmed: 23576424
Chembiochem. 2012 Jul 9;13(10):1447-57
pubmed: 22761035
Biochim Biophys Acta. 2015 Aug;1854(8):1019-37
pubmed: 25900361
Nat Commun. 2017 Apr 28;8:15172
pubmed: 28452358
J Antibiot (Tokyo). 2014 Jan;67(1):53-8
pubmed: 23921819
Nat Prod Rep. 2018 Apr 25;35(4):309-335
pubmed: 29359226
Org Lett. 2014 Jun 6;16(11):3072-5
pubmed: 24815182
Nat Prod Rep. 2014 Nov;31(11):1554-84
pubmed: 24965099
mBio. 2020 Feb 25;11(1):
pubmed: 32098813
Chembiochem. 2008 May 5;9(7):1136-45
pubmed: 18404760
ACS Chem Biol. 2018 Sep 21;13(9):2414-2420
pubmed: 30160099
Biochem Pharmacol. 2017 Jun 15;134:1-17
pubmed: 27984002
J Biol Chem. 2009 Oct 23;284(43):29746-56
pubmed: 19726666
Angew Chem Int Ed Engl. 2014 Oct 20;53(43):11645-9
pubmed: 25214315
Methods Enzymol. 2012;517:71-87
pubmed: 23084934
Angew Chem Int Ed Engl. 2010 Feb 15;49(8):1460-4
pubmed: 20033973
Environ Microbiol. 2017 Sep;19(9):3674-3688
pubmed: 28752961
J Mol Microbiol Biotechnol. 1999 Aug;1(1):33-43
pubmed: 10941782
Angew Chem Int Ed Engl. 2020 Dec 14;59(51):23122-23126
pubmed: 32588959
Nat Chem Biol. 2015 Dec;11(12):949-51
pubmed: 26479442
Nat Chem Biol. 2010 Feb;6(2):99-101
pubmed: 20081823
Ann N Y Acad Sci. 2015 Sep;1354:82-97
pubmed: 26509922
Chembiochem. 2003 Jul 7;4(7):654-7
pubmed: 12851937
Nat Commun. 2018 Jun 26;9(1):2478
pubmed: 29946103
Nat Prod Rep. 2004 Aug;21(4):519-38
pubmed: 15282634
Nat Rev Microbiol. 2012 Sep;10(9):641-54
pubmed: 22842661
Proc Natl Acad Sci U S A. 2007 Feb 13;104(7):2378-83
pubmed: 17277085
Nat Prod Rep. 2016 Feb;33(2):231-316
pubmed: 26689670
Angew Chem Int Ed Engl. 2020 Mar 27;59(14):5607-5610
pubmed: 31880848
Chem Biol. 2012 Jul 27;19(7):792-8
pubmed: 22840767