Transcriptomics identify the triggering of citrate export as the key event caused by manganese deficiency in <i>Aspergillus niger</i>

Citric acid is produced on industrial scale by batch fermentation of the filamentous fungus <i>Aspergillus niger</i>. High-yield citric acid production requires a low (<5 ppb) manganese(II) ion concentration in the culture broth. However, the requirement for this deficiency has not been investigated on a functional genomics level. Here, we compared the transcriptome of a citric acid hyper-producer <i>A. niger</i> strain grown under citric acid-producing conditions in 6-L scale bioreactors at Mn²⁺ ion-deficient (5 ppb) and Mn²⁺ ion-sufficient (100 ppb) conditions at three early time points of cultivation. We observed that Mn²⁺ deficiency triggers an upregulation of the citrate exporter gene cexA and provides functional evidence that this event is responsible for citrate overflow. In addition to the industrial relevance, this is the first study that examined the role of Mn²⁺ ion deficiency in a heterotrophic eukaryotic cell on a genome-wide scale.