AUTHOR=Sándor Erzsébet , Kolláth István S. , Fekete Erzsébet , Bíró Vivien , Flipphi Michel , Kovács Béla , Kubicek Christian P. , Karaffa Levente TITLE=Carbon-Source Dependent Interplay of Copper and Manganese Ions Modulates the Morphology and Itaconic Acid Production in Aspergillus terreus JOURNAL=Frontiers in Microbiology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.680420 DOI=10.3389/fmicb.2021.680420 ISSN=1664-302X ABSTRACT=

The effects of the interplay of copper(II) and manganese(II) ions on growth, morphology and itaconic acid formation was investigated in a high-producing strain of Aspergillus terreus (NRRL1960), using carbon sources metabolized either mainly via glycolysis (D-glucose, D-fructose) or primarily via the pentose phosphate shunt (D-xylose, L-arabinose). Limiting Mn²⁺ concentration in the culture broth is indispensable to obtain high itaconic acid yields, while in the presence of higher Mn²⁺ concentrations yield decreases and biomass formation is favored. However, this low yield in the presence of high Mn²⁺ ion concentrations can be mitigated by increasing the Cu²⁺ concentration in the medium when D-glucose or D-fructose is the growth substrate, whereas this effect was at best modest during growth on D-xylose or L-arabinose. A. terreus displays a high tolerance to Cu²⁺ which decreased when Mn²⁺ availability became increasingly limiting. Under such conditions biomass formation on D-glucose or D-fructose could be sustained at concentrations up to 250 mg L^–1 Cu²⁺, while on D-xylose- or L-arabinose biomass formation was completely inhibited at 100 mg L^–1. High (>75%) specific molar itaconic acid yields always coincided with an “overflow-associated” morphology, characterized by small compact pellets (<250 μm diameter) and short chains of “yeast-like” cells that exhibit increased diameters relative to the elongated cells in growing filamentous hyphae. At low concentrations (≤1 mg L^–1) of Cu²⁺ ions, manganese deficiency did not prevent filamentous growth. Mycelial- and cellular morphology progressively transformed into the typical overflow-associated one when external Cu²⁺ concentrations increased, irrespective of the available Mn²⁺. Our results indicate that copper ions are relevant for overflow metabolism and should be considered when optimizing itaconic acid fermentation in A. terreus.