Regulation of Heme Biosynthesis in Neurospora crassa

Abstract

The mold Neurospora crassa does not accumulate porphyrins in iron deficiency but instead accumulates the sideramine desferricoprogen. In iron deficiency there is an accumulation of δ-aminolevulinic acid and the δ-aminolevulinic acid dehydratase level is very low. A similar situation exists in cobalt toxicity and zinc deficiency. The δ-aminolevulinic acid synthetase and ferroprotoporphyrin chelatase comparatively show only marginal changes under these conditions. Addition of iron and zinc to the respective metal-deficient cultures results in an induction of δ-aminolevulinic acid dehydratase. The induction of δ-aminolevulinic acid dehydratase is repressed by protoporphyrin and less effectively by hemin and hemoglobin. Iron deficiency, zinc deficiency, and cobalt toxicity have been found to interfere with the conversion of protoporphyrin into heme, thus rendering protoporphyrin available to repress the enzyme. This repression can be counteracted by iron and much more effectively by coprogen. A model has been proposed in which protoporphyrin has been visualized as the corepressor for the enzyme δ-aminolevulinic acid dehydratase. It is held that iron in the form of coprogen converts protoporphyrin to heme, the latter having a lesser affinity for the aporepressor. Coprogen can inhibit heme binding to the aporepressor and thus render the repressor nonfunctional. This will lead to a derepression of the enzyme δ-aminolevulinic acid dehydratase.