Publication Date: 2017.
Nicotinate degradation has hitherto been elucidated only in bacteria. In the ascomycete Aspergillus nidulans, six loci, hxnS/AN9178 encoding the molybdenum cofactor-containing nicotinate hydroxylase, AN11197 encoding a Cys2/His2 zinc finger regulator HxnR, together with AN11196/hxnZ, AN11188/hxnY, AN11189/hxnP and AN9177/hxnT, are clustered and stringently co-induced by a nicotinate derivative and subject to nitrogen metabolite repression mediated by the GATA factor AreA. These genes are strictly co-regulated by HxnR. Within the hxnR gene, constitutive mutations map in two discrete regions. Aspergillus nidulans is capable of using nicotinate and its oxidation products 6-hydroxynicotinic acid and 2,5-dihydroxypyridine as sole nitrogen sources in an HxnR-dependent way. HxnS is highly similar to HxA, the canonical xanthine dehydrogenase (XDH), and has originated by gene duplication, preceding the origin of the Pezizomycotina. This cluster is conserved with some variations throughout the Aspergillaceae. Our results imply that a fungal pathway has arisen independently from bacterial ones. Significantly, the neo-functionalization of XDH into nicotinate hydroxylase has occurred independently from analogous events in bacteria. This work describes for the first time a gene cluster involved in nicotinate catabolism in a eukaryote and has relevance for the formation and evolution of co-regulated primary metabolic gene clusters and the microbial degradation of N-heterocyclic compounds.
Author affiliation: Ámon, Judit. University of Szeged. Faculty of Science and Informatics; Hungría
Author affiliation: Fernández y Martín, Rafael. Université Paris Sud; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Author affiliation: Bokor, Eszter. University of Szeged. Faculty of Science and Informatics; Hungría
Author affiliation: Cultrone, Antonietta. Université Paris Sud; Francia
Author affiliation: Kelly, Joan M.. University of Essex; Reino Unido
Author affiliation: Flipphi, Michel. Université Paris Sud; Francia
Author affiliation: Scazzocchio, Claudio. Université Paris Sud; Francia. University of Essex; Reino Unido. Imperial College London; Reino Unido
Author affiliation: Hamari, Zsuzsanna. Université Paris Sud; Francia. University of Szeged. Faculty of Science and Informatics; Hungría
Repository: CONICET Digital (CONICET). Consejo Nacional de Investigaciones Científicas y Técnicas