Regulation of hisHF Transcription of Aspergillus nidulans by Adenine and Amino Acid Limitation

Abstract The hisHF gene of Aspergillus nidulans encodes imidazole–glycerole–phosphate (IGP) synthase, consisting of a glutamine amidotransferase and a cyclase domain. The enzyme catalyzes the fifth and sixth steps of histidine biosynthesis, which results in an intermediate of the amino acid and an additional intermediate of purine biosynthesis. An A. nidulans hisHF cDNA complemented a Saccharomyces cerevisiae his7Δ strain and Escherichia coli hisH and hisF mutant strains. The genomic DNA encoding the hisHF gene was cloned and its sequence revealed two introns within the 1659-bp-long open reading frame. The transcription of the hisHF gene of A. nidulans is activated upon amino acid starvation, suggesting that hisHF is a target gene of cross pathway control. Adenine but not histidine, both end products of the biosynthetic pathways connected by the IGP synthase, represses hisHF transcription. In contrast to other organisms HISHF overproduction did not result in any developmental phenotype of the fungus in hyphal growth or the asexual life cycle. hisHF overexpression caused a significantly reduced osmotic tolerance and the inability to undergo the sexual life cycle leading to acleistothecial colonies.