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Metabolomics investigation of recombinant mTNFα production in Streptomyces lividans

Overview of attention for article published in Microbial Cell Factories, October 2015
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Title
Metabolomics investigation of recombinant mTNFα production in Streptomyces lividans
Published in
Microbial Cell Factories, October 2015
DOI 10.1186/s12934-015-0350-1
Pubmed ID
Authors

Howbeer Muhamadali, Yun Xu, David I. Ellis, Drupad K. Trivedi, Nicholas J. W. Rattray, Kristel Bernaerts, Royston Goodacre

Abstract

Whilst undergoing differentiation, Streptomyces produce a large quantity of hydrolytic enzymes and secondary metabolites, and it is this very ability that has focussed increasing interest on the use of these bacteria as hosts for the production of various heterologous proteins. However, within this genus, the exploration and understanding of the metabolic burden associated with such bio-products has only just begun. In this study our overall aim was to apply metabolomics approaches as tools to get a glimpse of the metabolic alterations within S. lividans TK24 when this industrially relevant microbe is producing recombinant murine tumour necrosis factor alpha (mTNFα), in comparison to wild type and empty (non-recombinant protein containing) plasmid-carrying strains as controls. Whilst growth profiles of all strains demonstrated comparable trends, principal component-discriminant function analysis of Fourier transform infrared (FT-IR) spectral data, showed clear separation of wild type from empty plasmid and mTNFα-producing strains, throughout the time course of incubation. Analysis of intra- and extra-cellular metabolic profiles using gas chromatography-mass spectrometry (GC-MS) displayed similar trends to the FT-IR data. Although the strain carrying the empty plasmid demonstrated metabolic changes due to the maintenance of the plasmid, the metabolic behaviour of the recombinant mTNFα-producing strain appeared to be the most significantly affected. GC-MS results also demonstrated a significant overflow of several organic acids (pyruvate, 2-ketoglutarate and propanoate) and sugars (xylitol, mannose and fructose) in the mTNFα-producing strain. The results obtained in this study have clearly demonstrated the metabolic impacts of producing mTNFα in S. lividans TK24, while displaying profound metabolic effects of harbouring the empty PIJ486 plasmid. In addition, the level of mTNFα produced in this study, further highlights the key role of media composition towards the efficiency of a bioprocess and metabolic behaviour of the host cells, which directly influences the yield of the recombinant product.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 42 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 42 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 8 19%
Student > Master 7 17%
Student > Ph. D. Student 6 14%
Student > Bachelor 4 10%
Professor 3 7%
Other 3 7%
Unknown 11 26%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 10 24%
Agricultural and Biological Sciences 9 21%
Chemical Engineering 3 7%
Nursing and Health Professions 2 5%
Veterinary Science and Veterinary Medicine 1 2%
Other 5 12%
Unknown 12 29%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 16 October 2015.
All research outputs
#13,755,002
of 22,829,683 outputs
Outputs from Microbial Cell Factories
#842
of 1,599 outputs
Outputs of similar age
#136,549
of 278,742 outputs
Outputs of similar age from Microbial Cell Factories
#22
of 47 outputs
Altmetric has tracked 22,829,683 research outputs across all sources so far. This one is in the 38th percentile – i.e., 38% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,599 research outputs from this source. They receive a mean Attention Score of 4.4. This one is in the 46th percentile – i.e., 46% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 278,742 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 50% of its contemporaries.
We're also able to compare this research output to 47 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 53% of its contemporaries.