This analysis showed

that iron, 5′-aminolevulinic acid (ALA) and possibly haem control haem biosynthesis mostly via modulating expression of hemA [coding for 5′-aminolevulinic acid synthase (ALAS)]. A hemA deletion mutant (ΔhemA) was constructed, which showed conditional lethality. Growth of ΔhemA was supported on standard nitrate-containing media with ALA, but not by hemin. Growth of ΔhemA could be sustained in the presence of hemin in combination with ammonium instead of nitrate as N-source. Our results suggest that a branch-off within the haem biosynthesis pathway required for sirohaem synthesis is responsible for lack of growth of ΔhemA in media containing nitrate as sole N-source, because of the requirement of sirohaem for nitrate assimilation, as a cofactor of nitrite reductase. In contrast to http://www.selleckchem.com/products/AZD2281(Olaparib).html the situation in Saccharomyces cerevisiae, cysteine, but not methionine, was found to further improve growth of ΔhemA. These results demonstrate that A. niger can use exogenous hemin for its cellular

processes. They also illustrate important differences in regulation of haem biosynthesis and in the role of haem and sirohaem in A. niger compared to S. cerevisiae. Haem is suggested to be a limiting factor in large-scale production of fungal peroxidases, which require this compound as a co-factor (Andersen et al., 1992; Elrod et al., 1997). Addition of hemin, a Cl-ligand of haem, to culture Selleckchem Epacadostat medium improves this production (Andersen et al., 1992; Elrod et al., 1997; Conesa et al., 2000), but is not suited for industrial applications (Elrod et al., 1997). Also, the mechanisms by which hemin supplementation improves peroxidase production are still unknown. To achieve improved and cost-effective

production of peroxidases by filamentous fungi, knowledge Selleck 5-Fluoracil on haem synthesis and regulation is required as current knowledge is mainly restricted to the first two genes in the pathway (Bradshaw et al., 1993; Elrod et al., 1997, 2000). Haem is an essential molecule for almost every organism owing to its requirement as a cofactor of proteins involved in many primary functions like cellular differentiation and gene regulation (Ferreira et al., 1993; Elrod et al., 1997; Panek & O’Brian, 2002; Hamza, 2006). Its biosynthesis in fungi has been extensively studied in Saccharomyces cerevisiae with mutants available for every step within the pathway (Gollub et al., 1977; Urban-Grimal & Labbe-Bois, 1981; Myers et al., 1987; Kurlandzka et al., 1988; Zagorec et al., 1988; Labbe-Bois, 1990; Keng et al., 1992; Amillet & Labbe-Bois, 1995; Camadro & Labbe, 1996; Hoffman et al., 2003). These mutants can be sustained by supplementing hemin to their growth media or by ergosterol or Tween80 addition to supply for essential unsaturated fatty acids (Gollub et al., 1977).