Targeting enzymes to the right compartment: metabolic engineering for itaconic acid production by Aspergillus niger

Metab Eng. 2013 Sep:19:26-32. doi: 10.1016/j.ymben.2013.05.003. Epub 2013 May 29.

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.

Keywords: AcoA; Aconitase; CadA; Microbial organic acid production; Mitochondrial targeting; cis-Aconitate decarboxylase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aconitate Hydratase / biosynthesis
  • Aconitate Hydratase / genetics
  • Aspergillus niger / genetics
  • Aspergillus niger / metabolism*
  • Carboxy-Lyases / biosynthesis
  • Carboxy-Lyases / genetics
  • Citric Acid / metabolism
  • Cytosol / metabolism
  • Fungal Proteins / biosynthesis
  • Fungal Proteins / genetics
  • Metabolic Engineering / methods
  • Mitochondria / enzymology
  • Mitochondria / genetics
  • Succinates / metabolism*

Substances

  • Fungal Proteins
  • Succinates
  • Citric Acid
  • Carboxy-Lyases
  • aconitate decarboxylase
  • Aconitate Hydratase
  • itaconic acid