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Streptomyces clavuligerus: The Omics Era

The Streptomyces clavuligerus genome consists in a linear chromosome of about 6.7 Mb and four plasmids (pSCL1 to pSCL4), the latter one of 1.8 Mb. Deletion of pSCL4, results in viable mutants with high instability in the chromosome arms, which may lead to chromosome circularisation. Transcriptomic a...

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Autores principales: Liras, Paloma, Martín, Juan F
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8788787/
https://www.ncbi.nlm.nih.gov/pubmed/34601575
http://dx.doi.org/10.1093/jimb/kuab072
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author Liras, Paloma
Martín, Juan F
author_facet Liras, Paloma
Martín, Juan F
author_sort Liras, Paloma
collection PubMed
description The Streptomyces clavuligerus genome consists in a linear chromosome of about 6.7 Mb and four plasmids (pSCL1 to pSCL4), the latter one of 1.8 Mb. Deletion of pSCL4, results in viable mutants with high instability in the chromosome arms, which may lead to chromosome circularisation. Transcriptomic and proteomic studies comparing different mutants with the wild-type strain improved our knowledge on the biosynthesis and regulation of clavulanic acid, cephamycin C and holomycin. Additional knowledge has been obtained on the SARP-type CcaR activator and the network of connections with other regulators (Brp, AreB, AdpA, BldG, RelA) controlling ccaR expression. The transcriptional pattern of the cephamycin and clavulanic acid clusters is supported by the binding of CcaR to different promoters and confirmed that ClaR is a CcaR-dependent activator that controls the late steps of clavulanic biosynthesis. Metabolomic studies allowed the detection of new metabolites produced by S. clavuligerus such as naringenin, desferroxamines, several N-acyl tunicamycins, the terpenes carveol and cuminyl alcohol or bafilomycin J. Heterologous expression of S. clavuligerus terpene synthases resulted in the formation of no less than 15 different terpenes, although none of them was detected in S. clavuligerus culture broth. In summary, application of the Omic tools results in a better understanding of the molecular biology of S. clavuligerus, that allows the use of this strain as an industrial actinobacterial platform and helps to improve CA production.
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spelling pubmed-87887872022-06-08 Streptomyces clavuligerus: The Omics Era Liras, Paloma Martín, Juan F J Ind Microbiol Biotechnol Genetics and Molecular Biology of Industrial Organisms The Streptomyces clavuligerus genome consists in a linear chromosome of about 6.7 Mb and four plasmids (pSCL1 to pSCL4), the latter one of 1.8 Mb. Deletion of pSCL4, results in viable mutants with high instability in the chromosome arms, which may lead to chromosome circularisation. Transcriptomic and proteomic studies comparing different mutants with the wild-type strain improved our knowledge on the biosynthesis and regulation of clavulanic acid, cephamycin C and holomycin. Additional knowledge has been obtained on the SARP-type CcaR activator and the network of connections with other regulators (Brp, AreB, AdpA, BldG, RelA) controlling ccaR expression. The transcriptional pattern of the cephamycin and clavulanic acid clusters is supported by the binding of CcaR to different promoters and confirmed that ClaR is a CcaR-dependent activator that controls the late steps of clavulanic biosynthesis. Metabolomic studies allowed the detection of new metabolites produced by S. clavuligerus such as naringenin, desferroxamines, several N-acyl tunicamycins, the terpenes carveol and cuminyl alcohol or bafilomycin J. Heterologous expression of S. clavuligerus terpene synthases resulted in the formation of no less than 15 different terpenes, although none of them was detected in S. clavuligerus culture broth. In summary, application of the Omic tools results in a better understanding of the molecular biology of S. clavuligerus, that allows the use of this strain as an industrial actinobacterial platform and helps to improve CA production. Oxford University Press 2021-10-02 /pmc/articles/PMC8788787/ /pubmed/34601575 http://dx.doi.org/10.1093/jimb/kuab072 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of Society of Industrial Microbiology and Biotechnology. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Genetics and Molecular Biology of Industrial Organisms
Liras, Paloma
Martín, Juan F
Streptomyces clavuligerus: The Omics Era
title Streptomyces clavuligerus: The Omics Era
title_full Streptomyces clavuligerus: The Omics Era
title_fullStr Streptomyces clavuligerus: The Omics Era
title_full_unstemmed Streptomyces clavuligerus: The Omics Era
title_short Streptomyces clavuligerus: The Omics Era
title_sort streptomyces clavuligerus: the omics era
topic Genetics and Molecular Biology of Industrial Organisms
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8788787/
https://www.ncbi.nlm.nih.gov/pubmed/34601575
http://dx.doi.org/10.1093/jimb/kuab072
work_keys_str_mv AT liraspaloma streptomycesclavuligerustheomicsera
AT martinjuanf streptomycesclavuligerustheomicsera