2019
DOI: 10.1016/j.fgb.2019.01.011
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The interplay between transport and metabolism in fungal itaconic acid production

Abstract: Besides enzymatic conversions, many eukaryotic metabolic pathways also involve transport proteins that shuttle molecules between subcellular compartments, or into the extracellular space. Fungal itaconate production involves two such transport steps, involving an itaconate transport protein (Itp), and a mitochondrial tricarboxylate transporter (Mtt). The filamentous actinomycete Aspergillus terreus and the unicellular basidiomycete Ustilago maydis both produce itaconate, but do so via very different molecular … Show more

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Cited by 29 publications
(35 citation statements)
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“…Interestingly, genes encoding Adi1 and Tad1 were found in all species with Um_Mtt1 ortholog while CadA‐encoding genes were found only in those expressing At_MttA (Table S2). These results suggest that the different IA biosynthetic pathways found in U. maydis and A. terreus may be connected to a different flux of substrates across the inner mitochondrial membrane catalyzed by Um_Mtt1 and At_MttA, as observed by transporter exchange experiments . The envisaged transport mechanism obtained in this paper can be helpful in the design of new metabolic engineering approaches with the aim of providing an increased amount of Mtt countersubstrates and thus improve itaconate production.…”
Section: Discussionmentioning
confidence: 60%
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“…Interestingly, genes encoding Adi1 and Tad1 were found in all species with Um_Mtt1 ortholog while CadA‐encoding genes were found only in those expressing At_MttA (Table S2). These results suggest that the different IA biosynthetic pathways found in U. maydis and A. terreus may be connected to a different flux of substrates across the inner mitochondrial membrane catalyzed by Um_Mtt1 and At_MttA, as observed by transporter exchange experiments . The envisaged transport mechanism obtained in this paper can be helpful in the design of new metabolic engineering approaches with the aim of providing an increased amount of Mtt countersubstrates and thus improve itaconate production.…”
Section: Discussionmentioning
confidence: 60%
“…The coding sequences for Um_Mtt1, optimized for its expression in Escherichia coli , and that for At_MttA, optimized for its expression in the fungus U. maydis , were amplified by PCR using the plasmids pMK‐UM05079 (GeneArt) and pETEF‐At_MttA , respectively, as templates. The Bam HI /Hind III Um_Mtt1 and At_MttA coding fragments were cloned into the E. coli expression vectors pET21b and pQE30 (QIAGEN Inc., Hilden, Germany), respectively, and transformed into E. coli DH5α‐T1 cells (Invitrogen, Carlsbad, CA, USA).…”
Section: Methodsmentioning
confidence: 99%
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“…In the previous experiment, the pH decreased from 6.5 to 3.68 for the ITA chassis. This likely affects itaconate productivity as U. maydis is not particularly tolerant to low pH (Hosseinpour Tehrani et al , ). In order to eliminate this potential pH inhibition, the buffer system was changed from MES to CaCO 3 and the substrate concentration was increased.…”
Section: Resultsmentioning
confidence: 99%
“…U. maydis represents a promising organism for application in industrial itaconate production. Recent efforts have achieved considerable improvements in itaconate production with Ustilago , including characterization and upregulation of the itaconate gene cluster and associated pathway (Geiser et al , ,c, ), engineering of transporters involved in itaconate production (Hosseinpour Tehrani et al , ), and morphological and metabolic engineering of the acid‐tolerant U. cynodontis (Hosseinpour Tehrani et al , ). However, the potpourri of metabolites naturally synthesized by U. maydis results in suboptimal specificity, productivity and yield of itaconate as a product.…”
Section: Introductionmentioning
confidence: 99%