Literature summary for 1.3.3.3 extracted from

Franken, A.C.; Werner, E.R.; Haas, H.; Lokman, B.C.; van den Hondel, C.A.; Ram, A.F.; de Weert, S.; Punt, P.J.
The role of coproporphyrinogen III oxidase and ferrochelatase genes in heme biosynthesis and regulation in Aspergillus niger (2013), Appl. Microbiol. Biotechnol., 97, 9773-9785 .

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Cloned(Commentary)

Cloned (Comment)	Organism
gene hemF, recombinant overexpression in Aspergillus niger, subcloning in Escherichia coli strain DH5alpha, complementation of a hemF deletion strain	Aspergillus niger

Protein Variants

Protein Variants	Comment	Organism
additional information	construction of a hemF and hemH deletion plasmids by transforming the linearized disruption vectors pDELTAhemF and pDELTAhemH into strain AB4.1, strain N402 genomic DNA is used as a template. Deletion of hemF (CPO) or hemH (FC) is conditionally lethal, and despite supplementation of hemin, DELTAhemF and DELTAhemH strains are still extremely impaired in growth. Co-overexpression of hemH, hemF, and the aminolevulinic acid synthase encoding hemA, increases the cellular accumulation of porphyrin intermediates suggesting regulatory mechanisms operating in the final steps of the fungal heme biosynthesis pathway. Gene hemF deletion strain displays a specific pigmented phenotype due to coproporphyrinogen III accumulation. Phenotypes, overview	Aspergillus niger

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
mitochondrion	-	Aspergillus niger	5739	-

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
coproporphyrinogen III + O2 + 2 H+	Aspergillus niger	-	protoporphyrinogen-IX + 2 CO2 + 2 H2O	-	?
coproporphyrinogen III + O2 + 2 H+	Aspergillus niger N402	-	protoporphyrinogen-IX + 2 CO2 + 2 H2O	-	?

Organism

Organism	UniProt	Comment	Textmining
Aspergillus niger	G3XZT7	-	-
Aspergillus niger N402	G3XZT7	-	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
hypha	-	Aspergillus niger	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
coproporphyrinogen III + O2 + 2 H+	-	Aspergillus niger	protoporphyrinogen-IX + 2 CO2 + 2 H2O	-	?
coproporphyrinogen III + O2 + 2 H+	-	Aspergillus niger N402	protoporphyrinogen-IX + 2 CO2 + 2 H2O	-	?

Synonyms

Synonyms	Comment	Organism
coproporphyrinogen III oxidase	-	Aspergillus niger
CPO	-	Aspergillus niger
HemF	-	Aspergillus niger

General Information

General Information	Comment	Organism
malfunction	the lethal phenotype of deletion of hemF can be remediated by heme supplementation confirming that Aspergillus niger is capable of hemin uptake. The hemF gene deletion mutant shows an extremely impaired growth even with hemin supplementation which can be slightly improved by media modifications and the use of hemoglobin as heme source. The hyphae of the mutant strains display pinkish coloration and red autofluorescence under UV indicative of cellular porphyrin accumulation. The mutant shows accumulation of specific porphyrins, thereby confirming the function of the protein in heme biosynthesis. Gene hemF deletion strain displays a specific pigmented phenotype due to coproporphyrinogen III accumulation. Phenotypes, overview	Aspergillus niger
metabolism	coproporphyrinogen III oxidase, CPO, is the sixth enzyme within the heme biosynthesis pathway, and is responsible for the oxidative decarboxylation of coproporphyrinogen III to protoporphyrinogen IX. Heme biosynthesis pathway, overview	Aspergillus niger
additional information	overexpression of hemH, but not hemF or the aminolevulinic acid synthase encoding hemA, modestly increases the cellular heme content, which is apparently insufficient to increase activity of endogenous peroxidase and cytochrome P450 enzyme activities. Overexpression of all three genes increases the cellular accumulation of porphyrin intermediates suggesting regulatory mechanisms operating in the final steps of the fungal heme biosynthesis pathway	Aspergillus niger
physiological function	in filamentous fungi, enzyme CPO functions as a regulatory step preventing hazardous levels of intracellular heme	Aspergillus niger

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Release 2023.1 (January 2023)