title: Heme biosynthesis and its regulation: towards understanding and improvement of heme biosynthesis in filamentous fungi.
abstract: Heme biosynthesis in fungal host strains has acquired considerable interest in relation to the production of secreted heme-containing peroxidases. Class II peroxidase enzymes have been suggested as eco-friendly replacements of polluting chemical processes in industry. These peroxidases are naturally produced in small amounts by basidiomycetes. Filamentous fungi like Aspergillus sp. are considered as suitable hosts for protein production due to their high capacity of protein secretion. For the purpose of peroxidase production, heme is considered a putative limiting factor. However, heme addition is not appropriate in large-scale production processes due to its high hydrophobicity and cost price. The preferred situation in order to overcome the limiting effect of heme would be to increase intracellular heme levels. This requires a thorough insight into the biosynthetic pathway and its regulation. In this review, the heme biosynthetic pathway is discussed with regards to synthesis, regulation, and transport. Although the heme biosynthetic pathway is a highly conserved and tightly regulated pathway, the mode of regulation does not appear to be conserved among eukaryotes. However, common factors like feedback inhibition and regulation by heme, iron, and oxygen appear to be involved in regulation of the heme biosynthesis pathway in most organisms. Therefore, they are the initial targets to be investigated in Aspergillus niger.
authors.affiliation: The Netherlands & Kluyver Centre for Genomics of Industrial Fermentation, PO Box 5057, 2600 GA Delft, The Netherlands.
authors.forename: Angelique C W
authors.initials: AC
authors.lastname: Franken
authors.forename: B Christien
authors.initials: BC
authors.lastname: Lokman
authors.forename: Arthur F J
authors.initials: AF
authors.lastname: Ram
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Punt
authors.forename: Cees A M J J
authors.initials: CA
authors.lastname: van den Hondel
authors.forename: Sandra
authors.initials: S
authors.lastname: de Weert
mesh_terms: D001234:Aspergillus niger / Q000378:metabolism*; D003067:Coenzymes / Q000378:metabolism; D005658:Fungi / Q000201:enzymology / Q000378:metabolism; D006418:Heme / Q000096:biosynthesis* / Q000235:genetics; D010544:Peroxidases / Q000378:metabolism
chemical_list: D003067:Coenzymes; D006418:Heme; D010544:Peroxidases