Effects of the pleiotropic regulator DasR on lincomycin production in Streptomyces lincolnensis.
S. lincolnensis
DasR
Lincomycin
Transcriptional regulators
Transcriptome analysis
Journal
Applied microbiology and biotechnology
ISSN: 1432-0614
Titre abrégé: Appl Microbiol Biotechnol
Pays: Germany
ID NLM: 8406612
Informations de publication
Date de publication:
15 Jun 2024
15 Jun 2024
Historique:
received:
17
01
2024
accepted:
22
05
2024
revised:
06
05
2024
medline:
15
6
2024
pubmed:
15
6
2024
entrez:
15
6
2024
Statut:
epublish
Résumé
The lincoamide antibiotic lincomycin, derived from Streptomyces lincolnensis, is widely used for the treatment of infections caused by gram-positive bacteria. As a common global regulatory factor of GntR family, DasR usually exists as a regulatory factor that negatively regulates antibiotic synthesis in Streptomyces. However, the regulatory effect of DasR on lincomycin biosynthesis in S. lincolnensis has not been thoroughly investigated. The present study demonstrates that DasR functions as a positive regulator of lincomycin biosynthesis in S. lincolnensis, and its overexpression strain OdasR exhibits a remarkable 7.97-fold increase in lincomycin production compared to the wild-type strain. The effects of DasR overexpression could be attenuated by the addition of GlcNAc in the medium in S. lincolnensis. Combined with transcriptome sequencing and RT-qPCR results, it was found that most structural genes in GlcNAc metabolism and central carbon metabolism were up-regulated, but the lincomycin biosynthetic gene cluster (lmb) were down-regulated after dasR knock-out. However, DasR binding were detected with the DasR responsive elements (dre) of genes involved in GlcNAc metabolism pathway through electrophoretic mobility shift assay, while they were not observed in the lmb. These findings will provide novel insights for the genetic manipulation of S. lincolnensis to enhance lincomycin production. KEY POINTS: • DasR is a positive regulator that promotes lincomycin synthesis and does not affect spore production • DasR promotes lincomycin production through indirect regulation • DasR correlates with nutrient perception in S. lincolnensis.
Identifiants
pubmed: 38878095
doi: 10.1007/s00253-024-13201-7
pii: 10.1007/s00253-024-13201-7
doi:
Substances chimiques
Lincomycin
BOD072YW0F
Anti-Bacterial Agents
0
Bacterial Proteins
0
Acetylglucosamine
V956696549
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
373Subventions
Organisme : 2021BEG02003
ID : 2021BEG02003
Informations de copyright
© 2024. The Author(s).
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