S47: The itaconic acid production gene cluster in Aspergillus terreus

A filamentous fungus Aspergillus terreus has been successfully used for producing itaconic acid in industry for many years. The gene, which encodes cis-aconitic acid decarboxylase (cad), is essential for itaconic acid production in A. terreus. To investigate the regulation of CAD enzyme function and the pathway for itaconic acid biosynthesis, bioinfomatic analysis of A. terreus genome was done and it is found there are 4 other important genes next to cad. Those genes are transcription factor (tf), mitochondrial organic acid transporter (mot), mfs and p450. Deletion strain of each gene was constructed and itaconic acid production was analyzed. In Dtf, the itaconic acid production dramatically decreased compared to wild type. After seven days of growth, itaconic acid level in Dtf decreases 7 fold. In Dmot, Dcad, itaconic acid is almost not detected. In Dmfs and Dtp450, itaconic acid is not affected much. In the Dtf strain, expression level of each gene was detected by RT-PCR. The transcription level of mot decreased 16 fold, cad showed 16 fold decrease, mfs decreased 8 fold and p450 was affected most, which had 300 fold decrease. For the first time, we demonstrated that a cluster, which are composed of tf, mot, cad, mfs and p450, play an important role in the itaconic acid biosynthesis pathway. tf is the key regulator for this cluster.