Cultrone Antonietta, Scazzocchio Claudio, Rochet Michel, Montero-Morán Gabriela, Drevet Christine, Fernández-Martín Rafael
Institut de Génétique et de Microbiologie, Université Paris-Sud, Bâtiment 409, UMR 8621 CNRS, 91405 Orsay Cedex, France.
Mol Microbiol. 2005 Jul;57(1):276-90. doi: 10.1111/j.1365-2958.2005.04686.x.
The xanthine oxidases and dehydrogenases are among the most conserved enzymes in all living kingdoms. They contain the molybdopterin cofactor Moco. We show here that in the fungi, in addition to xanthine dehydrogenase, a completely different enzyme is able to catalyse the oxidation of xanthine to uric acid. In Aspergillus nidulans this enzyme is coded by the xanA gene. We have cloned the xanA gene and determined its sequence. A deletion of the gene has the same phenotype as the previously known xanA1 miss-sense mutation. Homologues of xanA exist only in the fungal kingdom. We have inactivated the cognate gene of Schizosaccharomyces pombe and this results in strongly impaired xanthine utilization as a nitrogen source. We have shown that the Neurospora crassa homologue is functionally equivalent to xanA. The enzyme coded by xanA is an alpha-ketoglutarate- and Fe(II)-dependent dioxygenase which shares a number of properties with other enzymes of this group. This work shows that only in the fungal kingdom, an alternative mechanism of xanthine oxidation, not involving Moco, has evolved using the dioxygenase scaffold.
黄嘌呤氧化酶和脱氢酶是所有生物界中最保守的酶之一。它们含有钼蝶呤辅因子（Moco）。我们在此表明，在真菌中，除了黄嘌呤脱氢酶外，一种完全不同的酶能够催化黄嘌呤氧化为尿酸。在构巢曲霉中，这种酶由xanA基因编码。我们已经克隆了xanA基因并确定了其序列。该基因的缺失与先前已知的xanA1错义突变具有相同的表型。xanA的同源物仅存在于真菌界。我们已经使粟酒裂殖酵母的同源基因失活，这导致其作为氮源利用黄嘌呤的能力严重受损。我们已经表明，粗糙脉孢菌的同源物在功能上等同于xanA。由xanA编码的酶是一种依赖于α-酮戊二酸和Fe（II）的双加氧酶，它与该组中的其他酶具有许多共同特性。这项工作表明，仅在真菌界中，一种不涉及Moco的黄嘌呤氧化替代机制已经利用双加氧酶支架进化而来。
