Fabclavine diversity in Xenorhabdus bacteria
The global threat of multiresistant pathogens has to be answered by the development of novel antibiotics. Established antibiotic applications are often based on so-called secondary or specialized metabolites (SMs), identified in large screening approaches. To continue this successful strategy, new s...
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doaj-821e03fbf10b4688a31b44c77cfb83d92021-04-02T13:08:40ZengBeilstein-InstitutBeilstein Journal of Organic Chemistry1860-53972020-05-0116195696510.3762/bjoc.16.841860-5397-16-84Fabclavine diversity in Xenorhabdus bacteriaSebastian L. Wenski0Harun Cimen1Natalie Berghaus2Sebastian W. Fuchs3Selcuk Hazir4Helge B. Bode5Molekulare Biotechnologie, Fachbereich Biowissenschaften, Goethe Universität Frankfurt, Max-von-Laue-Str. 9, 60438 Frankfurt, GermanyAdnan Menderes University, Faculty of Arts and Sciences, Department of Biology, 09010 Aydin, TurkeyMolekulare Biotechnologie, Fachbereich Biowissenschaften, Goethe Universität Frankfurt, Max-von-Laue-Str. 9, 60438 Frankfurt, GermanyMolekulare Biotechnologie, Fachbereich Biowissenschaften, Goethe Universität Frankfurt, Max-von-Laue-Str. 9, 60438 Frankfurt, GermanyAdnan Menderes University, Faculty of Arts and Sciences, Department of Biology, 09010 Aydin, TurkeyMolekulare Biotechnologie, Fachbereich Biowissenschaften, Goethe Universität Frankfurt, Max-von-Laue-Str. 9, 60438 Frankfurt, GermanyThe global threat of multiresistant pathogens has to be answered by the development of novel antibiotics. Established antibiotic applications are often based on so-called secondary or specialized metabolites (SMs), identified in large screening approaches. To continue this successful strategy, new sources for bioactive compounds are required, such as the bacterial genera Xenorhabdus or Photorhabdus. In these strains, fabclavines are widely distributed SMs with a broad-spectrum bioactivity. Fabclavines are hybrid SMs derived from nonribosomal peptide synthetases (NRPS), polyunsaturated fatty acid (PUFA), and polyketide synthases (PKS). Selected Xenorhabdus and Photorhabdus mutant strains were generated applying a chemically inducible promoter in front of the suggested fabclavine (fcl) biosynthesis gene cluster (BGC), followed by the analysis of the occurring fabclavines. Subsequently, known and unknown derivatives were identified and confirmed by MALDI–MS and MALDI–MS2 experiments in combination with an optimized sample preparation. This led to a total number of 22 novel fabclavine derivatives in eight strains, increasing the overall number of fabclavines to 32. Together with the identification of fabclavines as major antibiotics in several entomopathogenic strains, our work lays the foundation for the rapid fabclavine identification and dereplication as the basis for future work of this widespread and bioactive SM class.https://doi.org/10.3762/bjoc.16.84antibioticfabclavinenrps-pks hybridsecondary metabolitexenorhabdus |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sebastian L. Wenski Harun Cimen Natalie Berghaus Sebastian W. Fuchs Selcuk Hazir Helge B. Bode |
spellingShingle |
Sebastian L. Wenski Harun Cimen Natalie Berghaus Sebastian W. Fuchs Selcuk Hazir Helge B. Bode Fabclavine diversity in Xenorhabdus bacteria Beilstein Journal of Organic Chemistry antibiotic fabclavine nrps-pks hybrid secondary metabolite xenorhabdus |
author_facet |
Sebastian L. Wenski Harun Cimen Natalie Berghaus Sebastian W. Fuchs Selcuk Hazir Helge B. Bode |
author_sort |
Sebastian L. Wenski |
title |
Fabclavine diversity in Xenorhabdus bacteria |
title_short |
Fabclavine diversity in Xenorhabdus bacteria |
title_full |
Fabclavine diversity in Xenorhabdus bacteria |
title_fullStr |
Fabclavine diversity in Xenorhabdus bacteria |
title_full_unstemmed |
Fabclavine diversity in Xenorhabdus bacteria |
title_sort |
fabclavine diversity in xenorhabdus bacteria |
publisher |
Beilstein-Institut |
series |
Beilstein Journal of Organic Chemistry |
issn |
1860-5397 |
publishDate |
2020-05-01 |
description |
The global threat of multiresistant pathogens has to be answered by the development of novel antibiotics. Established antibiotic applications are often based on so-called secondary or specialized metabolites (SMs), identified in large screening approaches. To continue this successful strategy, new sources for bioactive compounds are required, such as the bacterial genera Xenorhabdus or Photorhabdus. In these strains, fabclavines are widely distributed SMs with a broad-spectrum bioactivity. Fabclavines are hybrid SMs derived from nonribosomal peptide synthetases (NRPS), polyunsaturated fatty acid (PUFA), and polyketide synthases (PKS). Selected Xenorhabdus and Photorhabdus mutant strains were generated applying a chemically inducible promoter in front of the suggested fabclavine (fcl) biosynthesis gene cluster (BGC), followed by the analysis of the occurring fabclavines. Subsequently, known and unknown derivatives were identified and confirmed by MALDI–MS and MALDI–MS2 experiments in combination with an optimized sample preparation. This led to a total number of 22 novel fabclavine derivatives in eight strains, increasing the overall number of fabclavines to 32. Together with the identification of fabclavines as major antibiotics in several entomopathogenic strains, our work lays the foundation for the rapid fabclavine identification and dereplication as the basis for future work of this widespread and bioactive SM class. |
topic |
antibiotic fabclavine nrps-pks hybrid secondary metabolite xenorhabdus |
url |
https://doi.org/10.3762/bjoc.16.84 |
work_keys_str_mv |
AT sebastianlwenski fabclavinediversityinxenorhabdusbacteria AT haruncimen fabclavinediversityinxenorhabdusbacteria AT natalieberghaus fabclavinediversityinxenorhabdusbacteria AT sebastianwfuchs fabclavinediversityinxenorhabdusbacteria AT selcukhazir fabclavinediversityinxenorhabdusbacteria AT helgebbode fabclavinediversityinxenorhabdusbacteria |
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1724164235316953088 |