Secondary nucleotide messenger c-di-GMP exerts a global control on natural product biosynthesis in streptomycetes.
Bacterial Proteins
/ antagonists & inhibitors
Bambermycins
/ biosynthesis
Biological Products
/ metabolism
Cyclic GMP
/ analogs & derivatives
DNA-Binding Proteins
/ antagonists & inhibitors
Escherichia coli Proteins
/ genetics
Gene Deletion
Gene Expression Regulation, Bacterial
/ genetics
Nucleotides
/ genetics
Peptidoglycan Glycosyltransferase
/ antagonists & inhibitors
Phosphorus-Oxygen Lyases
/ genetics
Second Messenger Systems
/ genetics
Streptomycetaceae
/ genetics
Transcription Factors
/ antagonists & inhibitors
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
20 02 2020
20 02 2020
Historique:
accepted:
16
01
2020
revised:
17
12
2019
received:
16
08
2019
pubmed:
21
1
2020
medline:
20
3
2020
entrez:
21
1
2020
Statut:
ppublish
Résumé
Cyclic dimeric 3'-5' guanosine monophosphate, c-di-GMP, is a ubiquitous second messenger controlling diverse cellular processes in bacteria. In streptomycetes, c-di-GMP plays a crucial role in a complex morphological differentiation by modulating an activity of the pleiotropic regulator BldD. Here we report that c-di-GMP plays a key role in regulating secondary metabolite production in streptomycetes by altering the expression levels of bldD. Deletion of cdgB encoding a diguanylate cyclase in Streptomycesghanaensis reduced c-di-GMP levels and the production of the peptidoglycan glycosyltransferase inhibitor moenomycin A. In contrast to the cdgB mutant, inactivation of rmdB, encoding a phosphodiesterase for the c-di-GMP hydrolysis, positively correlated with the c-di-GMP and moenomycin A accumulation. Deletion of bldD adversely affected the synthesis of secondary metabolites in S. ghanaensis, including the production of moenomycin A. The bldD-deficient phenotype is partly mediated by an increase in expression of the pleiotropic regulatory gene wblA. Genetic and biochemical analyses demonstrate that a complex of c-di-GMP and BldD effectively represses transcription of wblA, thus preventing sporogenesis and sustaining antibiotic synthesis. These results show that manipulation of the expression of genes controlling c-di-GMP pool has the potential to improve antibiotic production as well as activate the expression of silent gene clusters.
Identifiants
pubmed: 31956908
pii: 5709707
doi: 10.1093/nar/gkz1220
pmc: PMC7026642
doi:
Substances chimiques
Bacterial Proteins
0
Biological Products
0
BldD protein, Streptomyces coelicolor
0
DNA-Binding Proteins
0
Escherichia coli Proteins
0
Nucleotides
0
Transcription Factors
0
Bambermycins
11015-37-5
moenomycin A
2RO799DN06
bis(3',5')-cyclic diguanylic acid
61093-23-0
Peptidoglycan Glycosyltransferase
EC 2.4.1.129
Phosphorus-Oxygen Lyases
EC 4.6.-
diguanylate cyclase
EC 4.6.1.-
Cyclic GMP
H2D2X058MU
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1583-1598Informations de copyright
© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.
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