Overexpression of isocitrate lyase-glyoxylate bypass influence on metabolism in Aspergillus niger

Susan Lisette Meijer, José Manuel Otero, Roberto Olivares Hernandez, Mikael Rørdam Andersen, Lisbeth Olsson, Jens Nielsen

    Research output: Contribution to journalJournal articleResearchpeer-review

    Abstract

    In order to improve the production of succinate and malate by the filamentous fungus Aspergillus niger the activity of the glyoxylate bypass pathway was increased by over-expression of the isocitrate lyase (icl) gene. The hypothesis was that when isocitrate lyase was up-regulated the flux towards glyoxylate would increase, leading to excess formation of malate and succinate compared to the wild-type. However, metabolic network analysis showed that an increased icl expression did not result in an increased glyoxylate bypass flux. The analysis did show a global response with respect to gene expression, leading to an increased flux through the oxidative part of the TCA cycle. Instead of an increased production of succinate and malate, a major increase in fumarate production was observed. The effect of malonate, a competitive inhibitor of succinate dehydrogenase (SDH), on the physiological behaviour of the cells was investigated. Inhibition of SDH was expected to lead to succinate production, but this was not observed. There was an increase in citrate and oxalate production in the wild-type strain. Furthermore, in the strain with over-expression of icl the organic acid production shifted from fumarate towards malate production when malonate was added to the cultivation medium. Overall, the icl over-expression and malonate addition had a significant impact on metabolism and on organic acid production profiles. Although the expected succinate and malate formation was not observed, a distinct and interesting production of fumarate and malate was found.
    Original languageEnglish
    JournalMetabolic Engineering
    Volume11
    Issue number2
    Pages (from-to)107-116
    ISSN1096-7176
    DOIs
    Publication statusPublished - 2009

    Keywords

    • Gene expression
    • Metabolic network analysis
    • Glyoxylate bypass
    • Reduced organic acids
    • Isocitrate lyase over-expression

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