LaeA controls citric acid production through regulation of a citrate exporter encoding cexA in Aspergillus luchuensis mut. kawachii

The putative methyltransferase LaeA is a global regulator of metabolic and development processes in filamentous fungi. We characterized the homologous laeA genes of the white koji fungus Aspergillus luchuensis mut. kawachii (A. kawachii) to determine their role in the hyperproduction of citric acid. The {Delta}laeA strain exhibited a significant reduction in citric acid productivity. Cap-analysis gene expression (CAGE) revealed that laeA is required for the gene expression of a putative citrate exporter encoding cexA, which is critical for citric acid production. The deficit in the productivity of citric acid by the {Delta}laeA strain was rescued by the overexpression of cexA to a level comparable with that of the cexA-overexpressing {Delta}cexA strain. In addition, chromatin immunoprecipitation coupled with quantitative PCR (ChIP-qPCR) analysis indicated that LaeA regulates the expression of cexA via methylation levels of the histones H3K4 and H3K9. These results indicate that LaeA is involved in citric acid production through epigenetic regulation of cexA in A. kawachii.\n\nIMPORTANCEA. kawachii has been traditionally used for production of the distilled spirit shochu in Japan. Citric acid produced by A. kawachii plays an important role in preventing microbial contamination during the shochu fermentation process. This study characterized homologous laeA genes; using CAGE, complementation test, and ChIP-qPCR, it was found that laeA is required for citric acid production though regulation of cexA in A. kawachii. The epigenetic regulation of citrate production elucidated in this study will be useful for controlling the fermentation processes of shochu.