Catabolism of Pyrimidines in Yeast

Abstract: Pyrimidines are important precursors for nucleic acids, and constantly synthesized and degraded in the cell to maintain a balanced supply. Many microoganisms can also extract the nitrogens from the pyrimidine ring, and use them as a nitrogen source when “preferred” sources are absent. Four different pathways, by which pyrimidines can be degraded, are known. I have studied the last discovered, but second most common one, called the URC pathway. It operates in several yeast and bacteria, and is so far the only complete degradation pathway found among yeast and fungi. The baker’s yeast, Saccharomyces cerevisiae is unable to degrade pyrimidines; however its distant relative, Lachancea kluyveri is able to utilize pyrimidines and their intermediates as a source of nitrogen. During my PhD project, I have studied the pyrimidine catabolism in L. kluyveri, in order to identify the genes involved, determine their function and how they are regulated. In total, six genes have been identified to take part in the utilization of uracil, and the function of URC8 has been determined. I have also characterized a specific regulatory protein of the pathway, Urc2p, and analyzed the overall regulation of the L. kluyveri genome in response to different sources of nitrogen, thereby finding evidence of nitrogen catabolite repression. In addition, intermediates of the pathway have been determined, and several transporters related to nitrogen metabolism have been investigated. In conclusion, the research presented in this thesis contributes to greater knowledge about the pyrimidine metabolism in yeast, although there are still details to be resolved in the future.