Integrated omics approaches provide strategies for rapid erythromycin yield increase in Saccharopolyspora erythraea

Microbial Cell Factories

Research

Jaka Horvat¹  Štefan Fujs¹  Katarina Karničar¹  Vasilka Magdevska¹  Gregor Kosec¹  Hrvoje Petković²  Igor Drobnak³  Marko Fonovič⁴  Boris Turk⁵  Robert Vidmar⁶  Marko Petek⁷  Špela Baebler⁷  Ana Rotter⁷  Kristina Gruden⁷  Polona Jamnik⁸ 

[1] Acies Bio, d.o.o., Tehnološki park 21, SI-1000, Ljubljana, Slovenia;Acies Bio, d.o.o., Tehnološki park 21, SI-1000, Ljubljana, Slovenia;Department of Food Science and Technology, Biotechnical Faculty, University of Ljubljana, Jamnikarjeva 101, SI-1000, Ljubljana, Slovenia;Acies Bio, d.o.o., Tehnološki park 21, SI-1000, Ljubljana, Slovenia;Department of Synthetic Biology and Immunology, National Institute of Chemistry, Hajdrihova 19, SI-1000, Ljubljana, Slovenia;Department of Biochemistry, Molecular and Structural Biology, Jožef Stefan Institute, Jamova cesta 39, SI-1000, Ljubljana, Slovenia;Centre of Excellence for Integrated Approaches in Chemistry and Biology of Proteins, Jamova cesta 39, SI-1000, Ljubljana, Slovenia;Department of Biochemistry, Molecular and Structural Biology, Jožef Stefan Institute, Jamova cesta 39, SI-1000, Ljubljana, Slovenia;Faculty of Chemistry and Chemical Technology, University of Ljubljana, Aškerčeva cesta 5, SI-1000, Ljubljana, Slovenia;Centre of Excellence for Integrated Approaches in Chemistry and Biology of Proteins, Jamova cesta 39, SI-1000, Ljubljana, Slovenia;Department of Biochemistry, Molecular and Structural Biology, Jožef Stefan Institute, Jamova cesta 39, SI-1000, Ljubljana, Slovenia;International Postgraduate School Jožef Stefan, Jamova cesta 39, SI-1000, Ljubljana, Slovenia;Department of Biotechnology and Systems Biology, National Institute of Biology, Večna pot 111, SI-1000, Ljubljana, Slovenia;Department of Food Science and Technology, Biotechnical Faculty, University of Ljubljana, Jamnikarjeva 101, SI-1000, Ljubljana, Slovenia;

关键词: Saccharopolyspora erythraea;    Erythromycin;    Systems biology;    Metabolic engineering;    Transcriptomics;    Proteomics;    Polyketide;    Substrate supply;   

DOI  :  10.1186/s12934-016-0496-5

 received in 2016-01-17, accepted in 2016-05-25,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundOmics 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.ResultsTo 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.ConclusionsOur 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.

【 授权许可】

CC BY   
© The Author(s) 2016