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

Paper ID Volume ID Publish Year Pages File Format Full-Text
31737 44834 2009 10 PDF Available
Title
Overexpression of isocitrate lyase—glyoxylate bypass influence on metabolism in Aspergillus niger
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.

Keywords
Isocitrate lyase over-expression; Glyoxylate bypass; Reduced organic acids; Metabolic network analysis; Gene expression
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Publisher
Database: Elsevier - ScienceDirect
Journal: Metabolic Engineering - Volume 11, Issue 2, March 2009, Pages 107–116
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
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Price was $35.95
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