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Title:Integrated omics approaches provide strategies for rapid erythromycin yield increase in Saccharopolyspora erythraea
Authors:ID Karničar, Katarina (Author)
ID Drobnak, Igor (Author)
ID Petek, Marko (Author)
ID Magdevska, Vasilka (Author)
ID Horvat, Jaka (Author)
ID Vidmar, Robert (Author)
ID Baebler, Špela (Author)
ID Rotter, Ana (Author)
ID Jamnik, Polona (Author)
ID Fujs, Štefan (Author)
ID Turk, Boris (Author)
ID Fonović, Marko (Author)
ID Gruden, Kristina (Author)
ID Kosec, Gregor (Author)
ID Petković, Hrvoje (Author)
Files:URL URL - Source URL, visit http://microbialcellfactories.biomedcentral.com/articles/10.1186/s12934-016-0496-5
 
.pdf PDF - Presentation file, download (3,06 MB)
MD5: 4D09F98BE6286B0D28E9ECC5618EB48E
 
Language:English
Typology:1.01 - Original Scientific Article
Organization:Logo NIB - National Institute of Biology
Logo IJS - Jožef Stefan Institute
Abstract:Background Omics approaches have significantly increased our understanding of biological systems. However, they have had limited success in explaining the dramatically increased productivity of commercially important natural products by industrial high-producing strains, such as the erythromycin-producing actinomycete Saccharopolyspora erythraea. Further yield increase is of great importance but requires a better understanding of the underlying physiological processes. Results To reveal the mechanisms related to erythromycin yield increase, we have undertaken an integrated study of the genomic, transcriptomic, and proteomic differences between the wild type strain NRRL2338 (WT) and the industrial high-producing strain ABE1441 (HP) of S. erythraea at multiple time points of a simulated industrial bioprocess. 165 observed mutations lead to differences in gene expression profiles and protein abundance between the two strains, which were most prominent in the initial stages of erythromycin production. Enzymes involved in erythromycin biosynthesis, metabolism of branched chain amino acids and proteolysis were most strongly upregulated in the HP strain. Interestingly, genes related to TCA cycle and DNA-repair were downregulated. Additionally, comprehensive data analysis uncovered significant correlations in expression profiles of the erythromycin-biosynthetic genes, other biosynthetic gene clusters and previously unidentified putative regulatory genes. Based on this information, we demonstrated that overexpression of several genes involved in amino acid metabolism can contribute to increased yield of erythromycin, confirming the validity of our systems biology approach. Conclusions Our comprehensive omics approach, carried out in industrially relevant conditions, enabled the identification of key pathways affecting erythromycin yield and suggests strategies for rapid increase in the production of secondary metabolites in industrial environment.
Keywords:aktinomicete, Saccharopolyspora erythraea, sekundarni metaboliti, antibiotiki, eritromicin, biosinteza, metabolno inženirstvo, proteomika
Publication status:Published
Publication version:Version of Record
Publication date:03.06.2016
Year of publishing:2016
Number of pages:str. 1/17-17/17
Numbering:Vol. 15, no. 93
PID:20.500.12556/DiRROS-19792 New window
UDC:604.4:615.332:579.873:577.2
ISSN on article:1475-2859
DOI:10.1186/s12934-016-0496-5 New window
COBISS.SI-ID:4655992 New window
Note:Soavtorji: Igor Drobnak, Marko Petek, Vasilka Magdevska, Jaka Horvat, Robert Vidmar, Špela Baebler, Ana Rotter, Polona Jamnik, Štefan Fujs, Boris Turk, Marko Fonovič, Kristina Gruden, Gregor Kosec, Hrvoje Petković; Nasl. z nasl. zaslona; Opis vira z dne 6. 6. 2016;
Publication date in DiRROS:25.07.2024
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Record is a part of a journal

Title:Microbial cell factories
Shortened title:Microb Cell Fact
Publisher:BioMed Central
ISSN:1475-2859
COBISS.SI-ID:2609172 New window

Document is financed by a project

Funder:ARIS - Slovenian Research and Innovation Agency
Project number:J4-2195-2009
Name:Preučevanje biosinteze eritromicina s proteomskimi orodji

Funder:ARIS - Slovenian Research and Innovation Agency
Project number:P1-0140-2015
Name:Proteoliza in njena regulacija

Funder:ARIS - Slovenian Research and Innovation Agency
Project number:J1-4121-2011
Name:Vloga cisteinskih katepsinov pri celičnem signaliziranju

Funder:ARIS - Slovenian Research and Innovation Agency
Project number:J4-4149-2011
Name:Preučevanje hom(e)olognih rekombinacij v evoluciji poliketidnih sintaz

Funder:Other - Other funder or multiple funders
Funding programme:European Regional Development Fund and the Government of Slovenia, Ministry of Education, Science and Sport
Name:“KC Brin competence centre” grant

Funder:Other - Other funder or multiple funders
Funding programme:European Social Fund and the Ministry of Economic Development and Technology
Project number:C2130-14-090124
Name:“KROP” Grant

Funder:Other - Other funder or multiple funders
Funding programme:Slovenian Technology Agency—TIA/SPIRIT
Project number:P-MR-09/103
Name:young researcher grant

Licences

License:CC BY 4.0, Creative Commons Attribution 4.0 International
Link:http://creativecommons.org/licenses/by/4.0/
Description:This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

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