Metabolic engineering of Yarrowia lipolytica for itaconic acid production

Blazeck, John; Hill, A.D.; Jamoussi, Mariam; Pan, Anny; Miller, Jarrett; Alper, Hal S.

doi:10.1016/j.ymben.2015.09.005

Cited by 124 publications

(81 citation statements)

References 43 publications

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“…A number of recombinant microorganisms, such as A. niger [51][52][53], Escherichia coli [28,56,68,92,102], Saccharomyces cerevisiae [6,39], Corynebacterium glutamicum [70], and Yarrowia lipolytica [7,95], have been developed over the last few years for production of IA (Table 2). However, most recombinant organisms were unable to produce IA titer equal to those produced by commercial A. terreus strains.…”

Section: Recombinant Microorganisms For Production Of Itaconic Acidmentioning

confidence: 99%

“…Blazeck et al [7] demonstrated the capacity to produce IA in Y. lipolytica through heterologous expression of the IA synthesis enzyme, resulting in an initial titer of 33 mg L −1 from glucose. Further optimization of this strain via metabolic pathway engineering, enzyme localization, and media optimization strategies enabled 4.6 g IA L −1 with an overall yield of 0.06 g g −1 glucose.…”

Section: Recombinant Microorganisms For Production Of Itaconic Acidmentioning

confidence: 99%

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Emerging biotechnologies for production of itaconic acid and its applications as a platform chemical

Saha¹

2017

Journal of Industrial Microbiology and Biotechnology

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Recently, itaconic acid (IA), an unsaturated C5-dicarboxylic acid, has attracted much attention as a biobased building block chemical. It is produced industrially (>80 g L) from glucose by fermentation with Aspergillus terreus. The titer is low compared with citric acid production (>200 g L). This review summarizes the latest progress on enhancing the yield and productivity of IA production. IA biosynthesis involves the decarboxylation of the TCA cycle intermediate cis-aconitate through the action of cis-aconitate decarboxylase (CAD) enzyme encoded by the CadA gene in A. terreus. A number of recombinant microorganisms have been developed in an effort to overproduce it. IA is used as a monomer for production of superabsorbent polymer, resins, plastics, paints, and synthetic fibers. Its applications as a platform chemical are highlighted. It has a strong potential to replace petroleum-based methylacrylic acid in industry which will create a huge market for IA.

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Section: Recombinant Microorganisms For Production Of Itaconic Acidmentioning

confidence: 99%

Section: Recombinant Microorganisms For Production Of Itaconic Acidmentioning

confidence: 99%

Emerging biotechnologies for production of itaconic acid and its applications as a platform chemical

Saha¹

2017

Journal of Industrial Microbiology and Biotechnology

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“…An atmospheric and room temperature plasma (ARTP) method has been applied for mutagenesis of various species to obtain targeted biological features (Zhang et al 2014;Kamath et al 2008). A Dietzia natronolimnaea mutant was isolated from samples treated with UV irradiation and EMS treatment for higher production of canthaxanthin (Gharibzahedi et al 2012), and mutants of Yarrowia lipolytica were obtained with significantly improved lipid production capacity (Blazeck et al 2015).…”

Section: Introductionmentioning

confidence: 99%

Combined mutagenesis of Rhodosporidium toruloides for improved production of carotenoids and lipids

et al. 2016

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“…Aspergillus terrous was the natural producer of itaconate, with a production level of 80 g/liter. After the gene encoding the key enzyme AtCAD was identified in 2008 (22), many studies were performed to utilize this gene to produce itaconate in various hosts, including Escherichia coli (33), Corynebacterium glutamicum (34), Saccharomyces cerevisiae (35), Yarrowia lipolytica (36), and A. niger. Because A. niger produced large amounts of citrate (180 g/liter), the precursor of itaconate, there was great interest in transforming the natural citrate producer into an itaconate producer; however, constitutive expression of the CAD gene alone led to only small amounts of itaconate production.…”

Section: Discussionmentioning

confidence: 99%

P gas , a Low-pH-Induced Promoter, as a Tool for Dynamic Control of Gene Expression for Metabolic Engineering of Aspergillus niger

Yin

Shin

et al. 2017

Appl Environ Microbiol

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The dynamic control of gene expression is important for adjusting fluxes in order to obtain desired products and achieve appropriate cell growth, particularly when the synthesis of a desired product drains metabolites required for cell growth. For dynamic gene expression, a promoter responsive to a particular environmental stressor is vital. Here, we report a low-pH-inducible promoter, Pgas, which promotes minimal gene expression at pH values above 5.0 but functions efficiently at low pHs, such as pH 2.0. First, we performed a transcriptional analysis of Aspergillus niger, an excellent platform for the production of organic acids, and we found that the promoter Pgas may act efficiently at low pH. Then, a gene for synthetic green fluorescent protein (sGFP) was successfully expressed by Pgas at pH 2.0, verifying the results of the transcriptional analysis. Next, Pgas was used to express the cis-aconitate decarboxylase (cad) gene of Aspergillus terreus in A. niger, allowing the production of itaconic acid at a titer of 4.92 g/liter. Finally, we found that Pgas strength was independent of acid type and acid ion concentration, showing dependence on pH only. IMPORTANCE The promoter Pgas can be used for the dynamic control of gene expression in A. niger for metabolic engineering to produce organic acids. This promoter may also be a candidate tool for genetic engineering.KEYWORDS Aspergillus niger, low-pH-inducible promoter, itaconic acid, dynamic gene expression, metabolic engineering A spergillus niger is an excellent cell factory for the production of organic acids (1). The rational engineering of A. niger has attracted increasing attention, and great achievements have been made in this area (2, 3). Nevertheless, because heterologous pathways are controlled by constitutive promoters, e.g., the promoter of the glyceraldehyde-3-phosphate dehydrogenase gene (gpdA), most of this research has focused on static metabolic engineering; that is, the gene expression level is set without sensing changes in the pathway output or cellular environment (4). One disadvantage of static control is related to the trade-off between growth and the production of a desired compound; suboptimal productivity is obtained because these pathways can drain metabolites required for biomass synthesis (5). Metabolic engineering approaches are being developed to tackle this problem via a dynamic control system to compensate for changing conditions (6). In this system, the cell modulates its metabolic pathways dynamically to adjust fluxes such that the required metabolic intermediates are delivered at the appropriate levels and times to optimize growth (7).

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Metabolic engineering of Yarrowia lipolytica for itaconic acid production

Cited by 124 publications

References 43 publications

Emerging biotechnologies for production of itaconic acid and its applications as a platform chemical

Emerging biotechnologies for production of itaconic acid and its applications as a platform chemical

Combined mutagenesis of Rhodosporidium toruloides for improved production of carotenoids and lipids

P gas , a Low-pH-Induced Promoter, as a Tool for Dynamic Control of Gene Expression for Metabolic Engineering of Aspergillus niger

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