Crp Is a Global Regulator of Antibiotic Production in <italic toggle="yes">Streptomyces</italic>

ABSTRACT Cyclic AMP receptor protein (Crp) is a transcription regulator controlling diverse cellular processes in many bacteria. In Streptomyces coelicolor, it is well established that Crp plays a critical role in spore germination and colony development. Here, we demonstrate that Crp is a key regul...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Chan Gao, Hindra, David Mulder, Charles Yin, Marie A. Elliot
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2012
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/c6ee16893fb845d9b7884c05009e99b5
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:c6ee16893fb845d9b7884c05009e99b5
record_format	dspace
spelling	oai:doaj.org-article:c6ee16893fb845d9b7884c05009e99b52021-11-15T15:39:11ZCrp Is a Global Regulator of Antibiotic Production in <italic toggle="yes">Streptomyces</italic>10.1128/mBio.00407-122150-7511https://doaj.org/article/c6ee16893fb845d9b7884c05009e99b52012-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00407-12https://doaj.org/toc/2150-7511ABSTRACT Cyclic AMP receptor protein (Crp) is a transcription regulator controlling diverse cellular processes in many bacteria. In Streptomyces coelicolor, it is well established that Crp plays a critical role in spore germination and colony development. Here, we demonstrate that Crp is a key regulator of secondary metabolism and antibiotic production in S. coelicolor and show that it may additionally coordinate precursor flux from primary to secondary metabolism. We found that crp deletion adversely affected the synthesis of three well-characterized antibiotics in S. coelicolor: actinorhodin (Act), undecylprodigiosin (Red), and calcium-dependent antibiotic (CDA). Using chromatin immunoprecipitation-microarray (ChIP-chip) assays, we determined that eight (out of 22) secondary metabolic clusters encoded by S. coelicolor contained Crp-associated sites. We followed the effect of Crp induction using transcription profiling analyses and found secondary metabolic genes to be significantly affected: included in this Crp-dependent group were genes from six of the clusters identified in the ChIP-chip experiments. Overexpressing Crp in a panel of Streptomyces species led to enhanced antibiotic synthesis and new metabolite production, suggesting that Crp control over secondary metabolism is broadly conserved in the streptomycetes and that Crp overexpression could serve as a powerful tool for unlocking the chemical potential of these organisms. IMPORTANCE Streptomyces produces a remarkably diverse array of secondary metabolites, including many antibiotics. In recent years, genome sequencing has revealed that these products represent only a small proportion of the total secondary metabolite potential of Streptomyces. There is, therefore, considerable interest in discovering ways to stimulate the production of new metabolites. Here, we show that Crp (the classical regulator of carbon catabolite repression in Escherichia coli) is a master regulator of secondary metabolism in Streptomyces. It binds to eight of 22 secondary metabolic gene clusters in the Streptomyces coelicolor genome and directly affects the expression of six of these. Deletion of crp in S. coelicolor leads to dramatic reductions in antibiotic levels, while Crp overexpression enhances antibiotic production. We find that the antibiotic-stimulatory capacity of Crp extends to other streptomycetes, where its overexpression activates the production of “cryptic” metabolites that are not otherwise seen in the corresponding wild-type strain.Chan GaoHindraDavid MulderCharles YinMarie A. ElliotAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 3, Iss 6 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Chan Gao Hindra David Mulder Charles Yin Marie A. Elliot Crp Is a Global Regulator of Antibiotic Production in <italic toggle="yes">Streptomyces</italic>
description	ABSTRACT Cyclic AMP receptor protein (Crp) is a transcription regulator controlling diverse cellular processes in many bacteria. In Streptomyces coelicolor, it is well established that Crp plays a critical role in spore germination and colony development. Here, we demonstrate that Crp is a key regulator of secondary metabolism and antibiotic production in S. coelicolor and show that it may additionally coordinate precursor flux from primary to secondary metabolism. We found that crp deletion adversely affected the synthesis of three well-characterized antibiotics in S. coelicolor: actinorhodin (Act), undecylprodigiosin (Red), and calcium-dependent antibiotic (CDA). Using chromatin immunoprecipitation-microarray (ChIP-chip) assays, we determined that eight (out of 22) secondary metabolic clusters encoded by S. coelicolor contained Crp-associated sites. We followed the effect of Crp induction using transcription profiling analyses and found secondary metabolic genes to be significantly affected: included in this Crp-dependent group were genes from six of the clusters identified in the ChIP-chip experiments. Overexpressing Crp in a panel of Streptomyces species led to enhanced antibiotic synthesis and new metabolite production, suggesting that Crp control over secondary metabolism is broadly conserved in the streptomycetes and that Crp overexpression could serve as a powerful tool for unlocking the chemical potential of these organisms. IMPORTANCE Streptomyces produces a remarkably diverse array of secondary metabolites, including many antibiotics. In recent years, genome sequencing has revealed that these products represent only a small proportion of the total secondary metabolite potential of Streptomyces. There is, therefore, considerable interest in discovering ways to stimulate the production of new metabolites. Here, we show that Crp (the classical regulator of carbon catabolite repression in Escherichia coli) is a master regulator of secondary metabolism in Streptomyces. It binds to eight of 22 secondary metabolic gene clusters in the Streptomyces coelicolor genome and directly affects the expression of six of these. Deletion of crp in S. coelicolor leads to dramatic reductions in antibiotic levels, while Crp overexpression enhances antibiotic production. We find that the antibiotic-stimulatory capacity of Crp extends to other streptomycetes, where its overexpression activates the production of “cryptic” metabolites that are not otherwise seen in the corresponding wild-type strain.
format	article
author	Chan Gao Hindra David Mulder Charles Yin Marie A. Elliot
author_facet	Chan Gao Hindra David Mulder Charles Yin Marie A. Elliot
author_sort	Chan Gao
title	Crp Is a Global Regulator of Antibiotic Production in <italic toggle="yes">Streptomyces</italic>
title_short	Crp Is a Global Regulator of Antibiotic Production in <italic toggle="yes">Streptomyces</italic>
title_full	Crp Is a Global Regulator of Antibiotic Production in <italic toggle="yes">Streptomyces</italic>
title_fullStr	Crp Is a Global Regulator of Antibiotic Production in <italic toggle="yes">Streptomyces</italic>
title_full_unstemmed	Crp Is a Global Regulator of Antibiotic Production in <italic toggle="yes">Streptomyces</italic>
title_sort	crp is a global regulator of antibiotic production in <italic toggle="yes">streptomyces</italic>
publisher	American Society for Microbiology
publishDate	2012
url	https://doaj.org/article/c6ee16893fb845d9b7884c05009e99b5
work_keys_str_mv	AT changao crpisaglobalregulatorofantibioticproductioninitalictoggleyesstreptomycesitalic AT hindra crpisaglobalregulatorofantibioticproductioninitalictoggleyesstreptomycesitalic AT davidmulder crpisaglobalregulatorofantibioticproductioninitalictoggleyesstreptomycesitalic AT charlesyin crpisaglobalregulatorofantibioticproductioninitalictoggleyesstreptomycesitalic AT marieaelliot crpisaglobalregulatorofantibioticproductioninitalictoggleyesstreptomycesitalic
_version_	1718427794107531264

Crp Is a Global Regulator of Antibiotic Production in <italic toggle="yes">Streptomyces</italic>

Ejemplares similares