Efficient itaconic acid production by Aspergillus terreus: Overcoming the strong inhibitory effect of manganese

Itaconic acid (IA), a building block platform chemical, is produced industrially by Aspergillus terreus utilizing glucose. Lignocellulosic biomass can serve as a low cost source of sugars for IA production. However, the fungus could not produce IA from dilute acid pretreated and enzymatically saccharified wheat straw hydrolyzate even at 100-fold dilution. Furfural, hydroxymethyl furfural and acetic acid were inhibitory, as is typical, but Mn²⁺ was particularly problematic for IA production. It was present in the hydrolyzate at a level that was 230 times over the inhibitory limit (50 ppb). Recently, it was found that PO₄³⁻ limitation decreased the inhibitory effect of Mn²⁺ on IA production. In the present study, a novel medium was developed for production of IA by varying PO₄³⁻, Fe³⁺ and Cu²⁺ concentrations using response surface methodology, which alleviated the strong inhibitory effect of Mn²⁺. The new medium contained 0.08 g KH₂PO₄, 3 g NH₄NO₃, 1 g MgSO₄·7H₂O, 5 g CaCl₂·2 H₂O, 0.83 mg FeCl₃·6H₂O, 8 mg ZnSO₄·7H₂O, and 45 mg CuSO₄·5H₂O per liter. The fungus was able to produce IA very well in the presence of Mn²⁺ up to 100 ppm in the medium. This medium will be extremely useful for IA production in the presence of Mn²⁺. This is the first report on the development of Mn²⁺ tolerant medium for IA production by A. terreus.