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Discovery and biosynthesis of bolagladins : unusual lipodepsipeptides from Burkholderia gladioli clinical isolates

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Dashti, Yousef, Nakou, Ioanna, Mullins, Alex, Webster, Gordon, Jian, Xinyun, Mahenthiralingam, Eshwar and Challis, Gregory L. (2020) Discovery and biosynthesis of bolagladins : unusual lipodepsipeptides from Burkholderia gladioli clinical isolates. Angewandte Chemie International Edition, 59 (48). pp. 21553-21561. doi:10.1002/anie.202009110

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Official URL: http://dx.doi.org/10.1002/anie.202009110

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Abstract

wo Burkholderia gladioli strains isolated from the lungs of cystic fibrosis patients were found to produce unusual lipodepsipeptides containing a unique citrate‐derived fatty acid and a rare dehydro‐β‐alanine residue. The gene cluster responsible for their biosynthesis was identified by bioinformatics and insertional mutagenesis. In‐frame deletions and enzyme activity assays were used to investigate the functions of several proteins encoded by the biosynthetic gene cluster, which was found in the genomes of about 50% of B. gladioli isolates, suggesting that its metabolic products play an important role in the growth and/or survival of the species. The Chrome Azurol S (CAS) assay indicated that these metabolites bind ferric iron, which suppresses their production when added to the growth medium. Moreover, a gene encoding a TonB‐dependent ferric‐siderophore receptor is adjacent to the biosynthetic genes, suggesting that these metabolites may function as siderophores in B. gladioli.

Item Type: Journal Article
Subjects: Q Science > QD Chemistry
Q Science > QH Natural history
Q Science > QP Physiology
Divisions: Faculty of Science > Chemistry
Library of Congress Subject Headings (LCSH): Natural products, Genomes, Peptides , Peptides -- Synthesis, Fatty acids, Biosynthesis
Journal or Publication Title: Angewandte Chemie International Edition
Publisher: Wiley - V C H Verlag GmbH & Co. KGaA
ISSN: 1433-7851
Official Date: 23 November 2020
Dates:
DateEvent
23 November 2020Published
11 August 2020Available
11 August 2020Accepted
Date of first compliant deposit: 4 September 2020
Volume: 59
Number: 48
Page Range: pp. 21553-21561
DOI: 10.1002/anie.202009110
Status: Peer Reviewed
Publication Status: Published
Publisher Statement: This is the peer reviewed version of the following article: Dashti, Y., Nakou, I., Mullins, A., Webster, G., Jian, X., Mahenthiralingam, E. and Challis, G. (2020), Discovery and biosynthesis of bolagladins: unusual lipodepsipeptides from Burkholderia gladioli clinical isolates. Angew. Chem. Int. Ed.. Accepted Author Manuscript. doi:10.1002/anie.202009110, which has been published in final form at http://dx.doi.org/10.1002/anie.202009110. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
Access rights to Published version: Open Access
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
BB/L021692/1 [BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
BB/L023342/1[BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
BB/S007652/1 [BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
BB/S008020/1[BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
MR/N501839/1 [MRC] Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
BB/M01116X/1[BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
LSBF R2-004Life Sciences Research Network WalesUNSPECIFIED
B/K002341/1[BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
WM130033Wolfson Foundationhttp://dx.doi.org/10.13039/501100001320

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