title: Targeting enzymes to the right compartment: metabolic engineering for itaconic acid production by Aspergillus niger.
abstract: Itaconic acid is an unsaturated dicarboxylic acid which has a high potential as a biochemical building block. It can be microbially produced from some Aspergillus species, such as Aspergillus itaconicus and Aspergillus terreus. However, the achieved titers are significantly lower as compared to the citric acid production by A. niger. Heterologous expression of cis-aconitate decarboxylase in A. niger leads to the accumulation of small amounts of itaconic acid. Additional expression of aconitase, the second enzyme metabolically linking citric acid and itaconic acid improves productivity. However, proper organelle targeting of the enzymes appears to be an important point to consider. Here we compare the mitochondrial expression with the cytosolic expression of cis-aconitate decarboxylase or aconitase in A. niger. Heterologous expression of both enzymes in the mitochondria doubles the productivity compared to strains which express the enzymes in the cytosol. It is essential to target enzymes to the correct compartment in order to establish a proper flux through a compartmentalized pathway.
authors.affiliation: Department of Biotechnology, BOKU-VIBT University of Natural Resources and Life Sciences, Vienna, Austria; School of Bioengineering, University of Applied Sciences FH-Campus Wien, Vienna, Austria. Electronic address: marzena.blumhoff@boku.ac.at.
authors.forename: Marzena L
authors.initials: ML
authors.lastname: Blumhoff
authors.forename: Matthias G
authors.initials: MG
authors.lastname: Steiger
authors.forename: Diethard
authors.initials: D
authors.lastname: Mattanovich
authors.forename: Michael
authors.initials: M
authors.lastname: Sauer
mesh_terms: D000154:Aconitate Hydratase / Q000096:biosynthesis / Q000235:genetics; D001234:Aspergillus niger / Q000235:genetics / Q000378:metabolism*; D002262:Carboxy-Lyases / Q000096:biosynthesis / Q000235:genetics; D019343:Citric Acid / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D005656:Fungal Proteins / Q000096:biosynthesis / Q000235:genetics; D060847:Metabolic Engineering / Q000379:methods; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics; D013386:Succinates / Q000378:metabolism*
chemical_list: D005656:Fungal Proteins; D013386:Succinates; D019343:Citric Acid; D002262:Carboxy-Lyases; C018742:aconitate decarboxylase; D000154:Aconitate Hydratase; C005229:itaconic acid
keywords: AcoA; Aconitase; CadA; Microbial organic acid production; Mitochondrial targeting; cis-Aconitate decarboxylase