Alternative Pathways for Siroheme Synthesis inKlebsiella aerogenes

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Abstract
Siroheme, the cofactor for sulfite and nitrite reductases, is formed by methylation, oxidation, and iron insertion into the tetrapyrrole uroporphyrinogen III (Uro-III). The CysG protein performs all three steps of siroheme biosynthesis in the enteric bacteriaEscherichia coliandSalmonella enterica. In either taxon,cysGmutants cannot reduce sulfite to sulfide and require a source of sulfide or cysteine for growth. In addition, CysG-mediated methylation of Uro-III is required for de novo synthesis of cobalamin (coenzyme B12) inS. enterica. We have determined thatcysGmutants of the related enteric bacteriumKlebsiella aerogeneshave no defect in the reduction of sulfite to sulfide. These data suggest that an alternative enzyme allows for siroheme biosynthesis in CysG-deficient strains ofKlebsiella. However,Klebsiella cysGmutants fail to synthesize coenzyme B12, suggesting that the alternative siroheme biosynthetic pathway proceeds by a different route. GenecysF, encoding an alternative siroheme synthase homologous to CysG, has been identified by genetic analysis and lies within thecysFDNCoperon; thecysFgene is absent from theE. coliandS. entericagenomes. While CysG is coregulated with the siroheme-dependent nitrite reductase, thecysFgene is regulated by sulfur starvation. Models for alternative regulation of the CysF and CysG siroheme synthases inKlebsiellaand for the loss of thecysFgene from the ancestor ofE. coliandS. entericaare presented.