A systems biology approach for the identification of target genes for the improvement of itaconic acid production in Aspergillus species

BACKGROUND: In this paper, a clone based transcriptome analysis towards the identification of genes related to itaconic acid production in Aspergillus terreus was carried out as an extension of a previously published a clone-based transcriptome analysis from a set of batch fermentation experiments. Also a publically available A. niger transcriptome dataset from cultures similar to those of the A. terreus data set was analyzed to evaluate the specificity of the approach followed for A. terreus. RESULTS: Besides the itaconic acid gene cluster (cis-aconitate decarboxylase, mitochondrial tri-carboxylic acid transporter and major facilitator superfamily transporter) discovered previously, additional genes of interest were identified in the A. terreus transcriptome data correlating to itaconic acid production, including 6 genes encoding enzymes in glycolysis and the pentose phosphate pathway, 4 genes functioning in vitamins synthesis, and a gene encoding a copper transporter. Only three of the 83 low pH specific genes identified from the A. niger dataset corresponded to high itaconic acid / low pH expressed genes identified from the A. terreus data set. However, in all three cases, the regulation of pH dependent gene expression was completely different between the two species. CONCLUSIONS: An extended clone based transcriptome analysis using a clone based transcription array to identify genes correlating with itaconic acid production revealed novel genes both in the central metabolism and in other more secondary pathways such as vitamin biosynthesis and Cu(2+) transport, providing targets for further metabolic and process engineering to optimize itaconic acid production.