Oxaloacetate hydrolase, the C-C bond lyase of oxalate secreting fungi

Y. Han, H.J. Joosten, W. Niu, Z. Zhao, P.S. Mariano, M. McCalman, J. van Kan, P.J. Schaap, D. Dunaway-Mariano

Research output: Contribution to journalArticleAcademicpeer-review

65 Citations (Scopus)

Abstract

Oxalate secretion by fungi is known to be associated with fungal pathogenesis. In addition, oxalate toxicity is a concern for the commercial application of fungi in the food and drug industries. Although oxalate is generated through several different biochemical pathways, oxaloacetate acetylhydrolase (OAH)-catalyzed hydrolytic cleavage of oxaloacetate appears to be an especially important route. Below, we report the cloning of the Botrytis cinerea oahA gene and the demonstration that the disruption of this gene results in the loss of oxalate formation. In addition, through complementation we have shown that the intact B. cinerea oahA gene restores oxalate production in an Aspergillus niger mutant strain, lacking a functional oahA gene. These observations clearly indicate that oxalate production in A. niger and B. cinerea is solely dependent on the hydrolytic cleavage of oxaloacetate catalyzed by OAH. In addition, the B. cinera oahA gene was overexpressed in Escherichia coli and the purified OAH was used to define catalytic efficiency, substrate specificity, and metal ion activation. These results are reported along with the discovery of the mechanism-based, tight binding OAH inhibitor 3,3-difluorooxaloacetate (Ki = 68 nM). Finally, we propose that cellular uptake of this inhibitor could reduce oxalate production
Original languageEnglish
Pages (from-to)9581-9590
JournalJournal of Biological Chemistry
Volume282
Issue number13
DOIs
Publication statusPublished - 2007

Keywords

  • oxalic-acid biosynthesis
  • petal death protein
  • aspergillus-niger
  • crystal-structure
  • isocitrate lyase
  • mycobacterium-tuberculosis
  • sclerotinia-sclerotiorum
  • 2-methylisocitrate lyase
  • oxalacetate
  • catalysis

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