Evidence map›Paper›PMID 26449894›Full record

ArticleMicrobial cell factories2015

Metabolomics investigation of recombinant mTNFα production in Streptomyces lividans.

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

Open access · goldAbstract read
In one paragraph

Article in Microbial cell factories, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.4field-weighted citation impact, top 20% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 22 citations in OpenAlex.

  1. Isolation ofInternational journal of microbiology · 2025
    Article
  2. Article
  3. Metabolomics ofInternational journal of molecular sciences · 2023
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  4. Metabolic Fingerprint Analysis of CytochromeFrontiers in microbiology · 2022
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  5. Article
  6. Review
  7. Radiation Tolerance ofFrontiers in microbiology · 2020
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Metabolic analysis of the response ofMetabolomics : Official journal of the Metabolomic Society
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 2 countries.

Howbeer MuhamadaliSchool of Chemistry, Manchester Institute of Biotechnology, University of Manchester, Manchester, UK. Howbeer.muhamadali@manchester.ac.uk.
Yun XuSchool of Chemistry, Manchester Institute of Biotechnology, University of Manchester, Manchester, UK. Yun.Xu-2@manchester.ac.uk.
David I EllisSchool of Chemistry, Manchester Institute of Biotechnology, University of Manchester, Manchester, UK. D.Ellis@manchester.ac.uk.
Drupad K TrivediSchool of Chemistry, Manchester Institute of Biotechnology, University of Manchester, Manchester, UK. drupad.trivedi@manchester.ac.uk.
Nicholas J W RattraySchool of Chemistry, Manchester Institute of Biotechnology, University of Manchester, Manchester, UK. nicholas.rattray@manchester.ac.uk.
Kristel BernaertsBio- and Chemical Systems Technology, Reactor Engineering and Safety, Department of Chemical Engineering, KU Leuven (University of Leuven), Leuven Chem&Tech, Celestijnenlaan 200F (bus 2424), 3001, Leuven, Belgium. Kristel.Bernaerts@cit.kuleuven.be.
Royston GoodacreSchool of Chemistry, Manchester Institute of Biotechnology, University of Manchester, Manchester, UK. roy.goodacre@manchester.ac.uk.
University of Manchester · GBKU Leuven · BE

Funding

Biotechnology and Biological Sciences Research Council BB/M017702/1
6 · The paper itself

Abstract

backgroundWhilst 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.

resultsWhilst 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.

conclusionThe 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.

Indexed as

MetabolomicsAnimalsDiscriminant AnalysisGas Chromatography-Mass SpectrometryMetabolomeMicePlasmidsPrincipal Component AnalysisRecombinant ProteinsSpectroscopy, Fourier Transform InfraredStreptomyces lividansTumor Necrosis Factor-alphaRecombinant ProteinsTumor Necrosis Factor-alpha

Identifiers

PMID26449894
PMCPMC4598958
OpenAlexW1931135204

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.