The benzodiazepine-like natural product tilivalline is produced by the entomopathogenic bacterium Xenorhabdus eapokensis

The pyrrolobenzodiazepine tilivalline (1) was originally identified in the human gut pathobiont Klebsiella oxytoca, the causative agent of antibiotic-associated hemorrhagic colitis. Here we show the identification of tilivalline and analogs thereof in the entomopathogenic bacterium Xenorhabdus eapok...

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Published in:PloS one 2018-03, Vol.13 (3), p.e0194297-e0194297
Main Authors: Wolff, Hendrik, Bode, Helge B
Format: Article
Language:English
Subjects:
Amino acids
Analogs
Antibiotics
Bacteria
Bacterial toxins
Benzodiazepines
Biochemistry
Biology and Life Sciences
Biosynthesis
Colitis
Computer and Information Sciences
Dehydrogenases
Deoxyribonucleic acid
DNA
Drug resistance
E coli
Enterobacteriaceae
Enzymes
Gene expression
Genes
Genetic aspects
Genomes
Hemorrhage
Identification and classification
Immune system
Klebsiella
Klebsiella oxytoca
Medicine and Health Sciences
Microbiological synthesis
Natural products
Peptides
Physical Sciences
Physiological aspects
Streptomyces
Xenorhabdus
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description The pyrrolobenzodiazepine tilivalline (1) was originally identified in the human gut pathobiont Klebsiella oxytoca, the causative agent of antibiotic-associated hemorrhagic colitis. Here we show the identification of tilivalline and analogs thereof in the entomopathogenic bacterium Xenorhabdus eapokensis as well as the identification of its biosynthesis gene cluster encoding a bimodular non-ribosomal peptide synthetase. Heterologous expression of both genes in E. coli resulted in the production of 1 and from mutasynthesis and precursor directed biosynthesis 11 new tilivalline analogs were identified in X. eapokensis. These results allowed the prediction of the tilivalline biosynthesis being similar to that in K. oxytoca.
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1932-6203
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subjects Amino acids
Analogs
Antibiotics
Bacteria
Bacterial toxins
Benzodiazepines
Biochemistry
Biology and Life Sciences
Biosynthesis
Colitis
Computer and Information Sciences
Dehydrogenases
Deoxyribonucleic acid
DNA
Drug resistance
E coli
Enterobacteriaceae
Enzymes
Gene expression
Genes
Genetic aspects
Genomes
Hemorrhage
Identification and classification
Immune system
Klebsiella
Klebsiella oxytoca
Medicine and Health Sciences
Microbiological synthesis
Natural products
Peptides
Physical Sciences
Physiological aspects
Streptomyces
Xenorhabdus
title The benzodiazepine-like natural product tilivalline is produced by the entomopathogenic bacterium Xenorhabdus eapokensis
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