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 protoporphyrin ring. The cytotoxicity of porphyrins suggests the need for coordination of its biosynthesis with iron availability. We isolated a mutant strain of the bacterium Bradyrhizobium japonicum that, under iron limitation, accumulated protoporphyrin and showed aberrantly high expression of hemB, an iron-regulated gene encoding the heme synthesis enzyme delta-aminolevulinic acid dehydratase. The strain carries a loss of function mutation in irr, a newly described gene that encodes a putative member of the GntR family of bacterial transcriptional regulators. Irr accumulated only under iron limitation, and turned over rapidly upon an increase in iron availability. A separate role for Irr in controlling the cellular iron level was inferred based on a deficiency in high affinity iron transport activity in the irr strain, and suggests that regulation of the heme pathway is coordinated with iron homeostasis. A high level of protoporphyrin accumulation is not a normal consequence of nutritional iron deprivation, thus a mechanism for iron-dependent control of heme biosynthesis may be present in other organisms.
Department of Biochemistry, State University of New York at Buffalo, Buffalo, New York 14214, USA.
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Hamza
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Chauhan
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Hassett
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O'Brian
D000595:Amino Acid Sequence; D001426:Bacterial Proteins; D006418:Heme / Q000096:biosynthesis*; D006706:Homeostasis; D007501:Iron / Q000378:metabolism*; D008969:Molecular Sequence Data; D011524:Protoporphyrins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012230:Rhizobiaceae / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D001426:Bacterial Proteins; D011524:Protoporphyrins; D012333:RNA, Messenger; D014157:Transcription Factors; C114259:iron response regulator protein, Bacteria; D006418:Heme; D007501:Iron