Pyrimidine biosynthesis genes in Aspergillus nidulans and the evolutionary origin of fungal dihydroorotases.0

Alexei Aleksenko, Wenguang Liu, Zoran Gojkovic, Jens Nielsen, and Jure Piskur.


The six biochemical steps of the de novo pyrimidine biosynthesis pathway are conserved in all known organisms. However, unlike in prokaryotes, in animals and fungi at least the first two activities are grouped on a multifunctional enzyme. In A. nidulans, the first two steps of the pathway are performed by a multifunctional enzyme comprising the activities of carbamoyl phosphate synthetase (CPSase) and aspartate transcarbamylase (ATCase). This polypeptide is encoded by a 7 kbp cluster gene, pyrABCN. The enzyme of the third step, dihydroorotase (DHOase), is encoded by a separate locus pyrD. However, the pyrABCN gene contains an evolutionary remnant of a DHOase-encoding sequence, which arrangement is similar to that in yeast. Comparison of amino acid sequences of active dihydroorotases with related enzymes indicates that the monofunctional dihydroorotases from fungi are more similar to ureases and enzymes of the pyrimidine degradation pathway, from which they have probably originated, than to DHOases of other organisms. The pyrABCN gene is transcribed as a single 7 kb mRNA species. The level of transcripts of pyrABCN, pyrD and, to a lesser degree, pyrF genes responds to the presence of exogenous pyrimidines and to the conditions of pyrimidine starvation. Derepression of pyrABCN and pyrD under pyrmidine starvation is noticeably enhanced in pyrE mutants which accumulate dihydroorotic acid. The data suggest that dihydroorotate is probably an inducer of at least some genes of the pathway, while UMP is a likely repressor. The cluster gene pyrABCN contains an upstream short open reading frame which may be involved in regulation. Some common features have been identified in promotor regions of pyr genes.

abstract No: 

Fungal Genet. Newsl. 46 (Supl):

Full conference title: 

Fungal Genetics Conference 20th
    • Fungal Genetics Conference 20th (1999)