THE BACTERIAL IRR PROTEIN IS REQUIRED FOR COORDINATION OF HEME-BIOSYNTHESIS WITH IRON AVAILABILITY

Heme is a ubiquitous macromolecule that serves as the active group of proteins involved in many cellular processes. The multienzyme pathway for heme formation culminates with the insertion of iron into a protop orphyrin ring. The cytotoxicity of porphyrins suggests the need for co ordination of its biosynthesis with iron availability. We isolated a m utant strain of the bacterium Bradyrhizobium japonicum that, under iro n limitation, accumulated protoporphyrin and showed aberrantly high ex pression of hemB, an iron-regulated gene encoding the heme synthesis e nzyme delta-aminolevulinic acid dehydratase. The strain carries a loss of function mutation in irr, a newly described gene that encodes a pu tative member of the GntR family of bacterial transcriptional regulato rs. Irr accumulated only under iron limitation, and turned over rapidl y upon an increase in iron availability. A separate role for Irr in co ntrolling the cellular iron level was inferred based on a deficiency i n high affinity iron transport activity in the irr strain, and suggest s that regulation of the heme pathway is coordinated with iron homeost asis. A high level of protoporphyrin accumulation is not a normal cons equence of nutritional iron deprivation, thus a mechanism for iron-dep endent control of heme biosynthesis may be present in other organisms.