Evidence map›Paper›PMID 27469970›Full record

ArticleMicrobial cell factories2016

Rewiring a secondary metabolite pathway towards itaconic acid production in Aspergillus niger.

Abeer H Hossain, An Li, Anja Brickwedde, Lars Wilms, Martien Caspers, Karin Overkamp, Peter J Punt

Open access · goldAbstract read
In one paragraph

Article in Microbial cell factories, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
5.2field-weighted citation impact, top 4% 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

31 citing papers in PubMed, 78 citations in OpenAlex.

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  3. Metabolic Engineering of Filamentous FungusJournal of agricultural and food chemistry · 2025
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  10. Conversion of COProceedings of the National Academy of Sciences of the United States of America · 2022
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  15. Review
  16. Review
  17. Metabolic engineering of an acid-tolerant yeast strainMetabolic engineering communications · 2020
    Article
  18. Article
  19. Biosynthesis of Alkylcitric Acids inFrontiers in microbiology · 2020
    Article
  20. Review
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 1 institution in 2 countries.

Abeer H HossainDutch DNA Biotech B.V, Utrechtseweg 48, 3704 HE, Zeist, The Netherlands. abeer.hossain@ddna-biotech.com.
An LiMicrobiology and Systems Biology, TNO, Utrechtseweg 48, 3704 HE, Zeist, The Netherlands.
Anja BrickweddeMicrobiology and Systems Biology, TNO, Utrechtseweg 48, 3704 HE, Zeist, The Netherlands.
Lars WilmsDutch DNA Biotech B.V, Utrechtseweg 48, 3704 HE, Zeist, The Netherlands.
Martien CaspersMicrobiology and Systems Biology, TNO, Utrechtseweg 48, 3704 HE, Zeist, The Netherlands.
Karin OverkampDutch DNA Biotech B.V, Utrechtseweg 48, 3704 HE, Zeist, The Netherlands.
Peter J PuntDutch DNA Biotech B.V, Utrechtseweg 48, 3704 HE, Zeist, The Netherlands.
Biotech Park · IN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe industrially relevant filamentous fungus Aspergillus niger is widely used in industry for its secretion capabilities of enzymes and organic acids. Biotechnologically produced organic acids promise to be an attractive alternative for the chemical industry to replace petrochemicals. Itaconic acid (IA) has been identified as one of the top twelve building block chemicals which have high potential to be produced by biotechnological means. The IA biosynthesis cluster (cadA, mttA and mfsA) has been elucidated in its natural producer Aspergillus terreus and transferred to A. niger to enable IA production. Here we report the rewiring of a secondary metabolite pathway towards further improved IA production through the overexpression of a putative cytosolic citrate synthase citB in a A. niger strain carrying the IA biosynthesis cluster.

resultsWe have previously shown that expression of cadA from A. terreus results in itaconic acid production in A. niger AB1.13, albeit at low levels. This low-level production is boosted fivefold by the overexpression of mttA and mfsA in itaconic acid producing AB1.13 CAD background strains. Controlled batch cultivations with AB1.13 CAD + MFS + MTT strains showed increased production of itaconic acid compared with AB1.13 CAD strain. Moreover, preliminary RNA-Seq analysis of an itaconic acid producing AB1.13 CAD strain has led to the identification of the putative cytosolic citrate synthase citB which was induced in an IA producing strain. We have overexpressed citB in a AB1.13 CAD + MFS + MTT strain and by doing so hypothesize to have targeted itaconic acid production to the cytosolic compartment. By overexpressing citB in AB1.13 CAD + MFS + MTT strains in controlled batch cultivations we have achieved highly increased titers of up to 26.2 g/L IA with a productivity of 0.35 g/L/h while no CA was produced.

conclusionsExpression of the IA biosynthesis cluster in Aspergillus niger AB1.13 strain enables IA production. Moreover, in the AB1.13 CAD strain IA production resulted in overexpression of a putative cytosolic citrate synthase citB. Upon overexpression of citB we have achieved titers of up to 26.2 g/L IA with a productivity of 0.35 g/L/h in controlled batch cultivations. By overexpressing citB we have also diminished side product formation and optimized the production pathway towards IA.

Indexed as

AspergillusAspergillus nigerCitrate (si)-SynthaseCloning, MolecularFermentationGene Transfer TechniquesMetabolic Networks and PathwaysSuccinatesCitrate (si)-Synthaseitaconic acidSuccinatescitBCitric acidControlled-batch cultivationItaconic acidSecondary metabolite

Identifiers

PMID27469970
PMCPMC4965889
OpenAlexW2480817305

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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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.