title: Thiamine synthesis regulates the fermentation mechanisms in the fungus Aspergillus nidulans.
abstract: Thiamine pyrophosphate (TPP) is a critical cofactor and its biosynthesis is under the control of TPP availability. Here we disrupted a predicted thiA gene of the fungus Aspergillus nidulans and demonstrated that it is essential for synthesizing cellular thiamine. The thiamine riboswitch is a post-transcriptional mechanism for TPP to repress gene expression and it is located on A. nidulans thiA pre-messenger RNA. The thiA riboswitch was not fully derepressed under thiamine-limited conditions, and fully derepressed under environmental stressors. Upon exposure to hypoxic stress, the fungus accumulated more ThiA and NmtA proteins, and more thiamine than under aerobic conditions. The thiA gene was required for the fungus to upregulate hypoxic branched-chain amino acids and ethanol fermentation that involve enzymes containing TPP. These findings indicate that hypoxia modulates thiA expression through the thiamine riboswitch, and alters cellular fermentation mechanisms by regulating the activity of the TPP enzymes.
authors.affiliation: a Faculty of Life and Environmental Sciences , University of Tsukuba , Tsukuba , Japan.|b Faculty of Agriculture, Department of Applied Biological Chemistry , Meijo University , Nagoya , Japan.
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Shimizu
authors.affiliation: a Faculty of Life and Environmental Sciences , University of Tsukuba , Tsukuba , Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Masuo
authors.affiliation: a Faculty of Life and Environmental Sciences , University of Tsukuba , Tsukuba , Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Itoh
authors.affiliation: a Faculty of Life and Environmental Sciences , University of Tsukuba , Tsukuba , Japan.
authors.forename: Shengmin
authors.initials: S
authors.lastname: Zhou
authors.affiliation: b Faculty of Agriculture, Department of Applied Biological Chemistry , Meijo University , Nagoya , Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Kato
authors.affiliation: a Faculty of Life and Environmental Sciences , University of Tsukuba , Tsukuba , Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Takaya
mesh_terms: D001233:Aspergillus nidulans / Q000201:enzymology*; D015687:Cell Hypoxia; D005285:Fermentation; D005656:Fungal Proteins / Q000096:biosynthesis / Q000235:genetics*; D015966:Gene Expression Regulation, Fungal; D058928:Riboswitch / Q000235:genetics*; D013312:Stress, Physiological / Q000235:genetics; D013831:Thiamine / Q000096:biosynthesis* / Q000235:genetics; D013835:Thiamine Pyrophosphate / Q000096:biosynthesis / Q000235:genetics
chemical_list: D005656:Fungal Proteins; D058928:Riboswitch; D013835:Thiamine Pyrophosphate; D013831:Thiamine
keywords: alcohol fermentation; branched-chain amino acid; stress; thiazole synthesis