User:Matthew Whiteside/Notebook/Fumigatus Microarray/2009/03/18

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Iron effect on metabolism in fumigatus

Hypothesis: changes in iron modulates citric acid cycle, in the following ways (based on SreA study)

  1. Direct repression of anaplerotic rxn enzymes & transporters through SreA (anaplerotic rxn replenish TCA intermediates that are used in biosynthesis rxn). Genes regulated by SreA, related to anaplerotic rxns are:
    • GABA permease 5g00710 (part of cluster that is down-reg in Fe-replete conditions)
    • NAD-dependent formate dehydrogenase 6g04920
    • Beta-IPM (isopropylmalate) dehydrogenase 6g13590 (oxalic intermediate)
  2. Direct repression of glycogen & alt sugar utilization. Genes regulated by SreA (caution: little supporting evidence):
    • Glycogen phosphorylase 1g12920
    • L-arabitol dehydrogenase 3g01490
  3. Indirect repression of anaplerotic rxn enzymes & transporters. Genes repressed during iron-replete conditions:
    • GABA:
      • 3g07150
  4. Indirect repression of anaplerotic rxn enzymes & transporters. Genes up-regulated during iron-replete conditions (some withincreased up-reg with intact SreA*):
    • GABA:
      • 4g08170*
      • 5g06680*
    • Oxalic acid:
      • 7g01010*
      • 2g03820
  5. Indirect action on glycogen & alt sugar utilization (didn't go into details)

There appears to be complex transcriptional control mediated by iron conditions. In a few cases, SreA appears to directly repress some genes.