Promoter Activation in Δhfq Mutants as an Efficient Tool for Specialized Metabolite Production Enabling Direct Bioactivity Testing.
bioactivity testing
easyPACId
natural products
proteobacteria
simplified production
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:
19 12 2019
19 12 2019
Historique:
received:
31
08
2019
pubmed:
7
11
2019
medline:
25
9
2020
entrez:
7
11
2019
Statut:
ppublish
Résumé
Natural products (NPs) from microorganisms have been important sources for discovering new therapeutic and chemical entities. While their corresponding biosynthetic gene clusters (BGCs) can be easily identified by gene-sequence-similarity-based bioinformatics strategies, the actual access to these NPs for structure elucidation and bioactivity testing remains difficult. Deletion of the gene encoding the RNA chaperone, Hfq, results in strains losing the production of most NPs. By exchanging the native promoter of a desired BGC against an inducible promoter in Δhfq mutants, almost exclusive production of the corresponding NP from the targeted BGC in Photorhabdus, Xenorhabdus and Pseudomonas was observed including the production of several new NPs derived from previously uncharacterized non-ribosomal peptide synthetases (NRPS). This easyPACId approach (easy Promoter Activated Compound Identification) facilitates NP identification due to low interference from other NPs. Moreover, it allows direct bioactivity testing of supernatants containing secreted NPs, without laborious purification.
Identifiants
pubmed: 31693786
doi: 10.1002/anie.201910563
pmc: PMC6972681
doi:
Substances chimiques
Biological Products
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
18957-18963Subventions
Organisme : LOEWE-Centre Translational Biodiversity Genomics
ID : LOEWE TBG
Pays : International
Organisme : Scientific and Technological Research Council of Turkey (TUBITAK)
ID : TOVAG-117O172
Pays : International
Organisme : LOEWE-Centre Translational Medicine and Pharmacology
ID : LOEWE TMP
Pays : International
Organisme : LOEWE-Centre Insect Biotechnology and Bioressources
ID : LOEWE Insect biotechnology
Pays : International
Organisme : LOEWE research cluster MegaSyn
ID : LOEWE MegaSyn
Pays : International
Organisme : DFG
ID : INST 161/810-1
Pays : International
Informations de copyright
© 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.
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