The DOI matches its Crossref record; 59 of the 69 references it cites were found in a registry or an index.
Biotechnological production of itaconic acid and its biosynthesis in Aspergillus terreus
Open accessAbstract
More than 80,000 tons of itaconic acid (IA) is produced worldwide each year and is sold at a price of around US$ 2/kg. The IA production yield from sugar is higher than 80 g/l. The widespread use of IA in synthetic resins, synthetic fibers, plastics, rubbers, surfactants, and oil additives has resulted in an increased demand for this product. However, at present, the IA production capacity exceeds the demand because this product has a restricted range of applications. Studies have been actively conducted in different biomedical fields--dental, ophthalmic, and drug delivery--to extend the range of applications of IA. Recently, many researchers have attempted to replace the carbon source used for microbial production of IA with cheaper alternative substrates. However, there is still a need for new biotechnology innovations that would help to reduce the production costs, such as innovative process development and strain improvement to allow the use of a low-quality carbon source. In this short review, we discuss the following aspects of IA production: strain improvement, process development, identification of the key enzyme cis-aconitic acid decarboxylase (CAD) in the IA metabolic pathway, metabolic importance of CAD, and new applications of IA.
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In the citing paper
“DI was first employed as an experimental tool and was shown to potently induce Nrf2 and several Nrf2 target genes in control and LPS-activated BMDMs59.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [59]
In the citing paper
“Since 2016, several key studies have uncovered a role for itaconate as a crucial anti-inflammatory metabolite that negatively regulates the inflammatory response and cytokine production50,59–61, as shown in Figure 3.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [59]
In the citing paper
“DI was shown to significantly and acutely deplete GSH levels, confirming it was indeed an activated Michael acceptor59.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [59]
In the citing paper
“itaconate and 4-OI were shown to have a similar thiol reactivity profile”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [59]
In the citing paper
“the ability of 4-OI to induce NQO1 activity remained unaffected59.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [59]
In the citing paper
“the induction of Irg1 and itaconate was largely dependent on autocrine/paracrine type I interferon signalling59.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [59]
In the citing paper
“pre-treatment of control and LPS-activated macrophages with 4-OI still resulted in a significant increase in Nrf2 and Nrf2 target genes, namely Heme oxygenase 1 (HMOX1)”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [59]
In the citing paper
“Further supporting the hypothesis that itaconate was a thiol reactive metabolite, a significant increase in the levels of the metabolite 2,3-dicarboxypropyl cysteine (itaconate-cysteine adduct), akin to (S)-2-succinocysteine (2SC) a breakdown product of fumarate-mediated protein succination, was observed in LPS-activated BMDMs59.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [59]
In the citing paper
“Pre-treatment of LPS-activated BMDMs with 4-OI also resulted in a significant attenuation of IL-1β levels”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [59]
In the citing paper
“4-OI was shown to alkylate KEAP1 on several cysteine residues, namely cysteine 151 (C151), a principal redox sensing cysteine important for activation of Nrf259,66.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [59]
In the citing paper
“Furthermore, using a quantitative unbiased proteomic screen performed in both LPS (which will drive intracellular itaconate accumulation) and 4-OI-treated macrophages, several metabolic and inflammatory proteins were found to be alkylated representing the first demonstration of this novel post-translational modification (PTM), termed 2,3-dicarboxypropylation59.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [59]
In the citing paper
“pre-treatment of LPS-activated macrophages with 4-OI resulted in a significant attenuation of IFN-β levels and interferon-stimulated genes (ISGs), namely ISG20”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [59]
In the citing paper
“an effect that was at least partially dependent on Nrf259.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [59]
In the citing paper
“the ability of DI to induce NQO1 activity (a prototypical Nrf2 target gene) was diminished when pre-incubated with GSH”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [59]
In the citing paper
“an effect that was largely abrogated in Nrf2-deficent macrophages59.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [59]
In the citing paper
“4-OI was also shown to be protective in an LPS lethality model in vivo, prolonging survival, improving body temperature regulation and decreasing pro-inflammatory cytokine production59.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [59]
In the citing paper
“ACLY is phosphorylated downstream of AKT activation, following DNA damage and this facilitates histone acetylation at double strand break (DSB) sites, enabling breast cancer early onset 1 (BRCA1) recruitment and DNA repair by homologous recombination.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [59]
In the citing paper
“ACLY, acetyl-CoA levels and histone acetylation have also been shown to play an important role in the DNA damage response in tumor cells 59.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [59]
In the citing paper
“ACLY deficiency results in impaired BRCA1 recruitment to sites of DSBs and suppression of homologous recombination.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [59]
In the citing paper
“The generation of itaconate from the Krebs Cycle intermediate cis-aconitate contrasts with most other metabolite signals emanating from mitochondria, in that it primarily acts as a protective, anti-inflammatory metabolite55,59,60.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [59]
In the citing paper
“4-OI is an itaconate mimic that was protective in a mouse model of sepsis, decreasing cytokine production and increasing survival59.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [59]
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Metadata
- Authors
- Okabe, M., Lies, D., Kanamasa, S., & Park, E. Y.
- Affiliations
- Musashino Chemical Laboratory, Ltd. (Japan) (JP)
- Chubu University (JP)
- Shizuoka University (JP)
- Corresponding author
- Park, Enoch Y.
- Venue
- Applied Microbiology and Biotechnology
- Published
- 2009-07-21
- Volume
- 84
- Issue
- 4
- Pages
- 597-606
- ISSN
- 0175-7598 (ISSN-L)
- 1432-0614
- OpenAlex
- W2169769082
- Cited by
- 488
- References
- 69
- Citations by year
- 2026: 9 · 2025: 28 · 2024: 35 · 2023: 38 · 2022: 30 · 2021: 35 · 2020: 40 · 2019: 46 · 2018: 28 · 2017: 39 · 2016: 41 · 2015: 30 · 2014: 30 · 2013: 26 · 2012: 15
- FWCI
- 0.81
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- cc-by-nc-nd
- www.springer.com/tdm (tdm)
- Locations
- Applied Microbiology and Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- Shizuoka University Repository (Shizuoka University) (submittedVersion, cc-by-nc-nd)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Biochemical and biochemical processes
- Life Sciences › Immunology and Microbiology › Applied Microbiology and Biotechnology › Microbial Natural Products and Biosynthesis
- Keywords
- itaconic acid, Aspergillus terreus, strain improvement, fermentation process development, metabolic pathways, biopolymer applications, dental applications, drug delivery
- MeSH terms
- Aspergillus, Genetic Engineering, Succinates, Biosynthetic Pathways
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