The genetic control of molybdoflavoproteins in Aspergillus nidulans. Allopurinol-resistant mutants constitutive for xanthine-dehydrogenase.

Abstract

This paper describes the isolation and properties of a class of mutants (apl Ac), constitutive for the enzyme xanthine dehydrogenase. These mutants are superinducible and semidominant. Four independently isolated strains carry constitutive mutations which are allelic.Strains carrying the apl Ac mutation are, as the wild type, repressible by ammonia, and at variance with the wild type repressible by nitrate. The apl Ac mutation suppress mutations at the hx A locus that result in loss of xanthine dehydrogenase, and the ua Y locus that result in non‐inducibility for both xanthine dehydrogenase and urate oxidase, but only for xanthine dehydrogenase. Immunological evidence shows that the apl Ac mutation results in the production of a xanthine dehydrogenase (II) different from the one nom rally induced in the wild type by uric acid (I). Genetic evidence shows that whereas the hx A locus codes for a product specific for xanthine dehydrogenase I the hx B locus codes for a product necessary for both xanthine dehydrogenases I and II and that the cnx loci code for a cofactor present in xanthine dehydrogenase I and II and nitrate reductase. A model is presented by which xanthine dehydrogenase I and II are formed by a core comprising the polypeptide coded by the hx B locus and the cofactor specified by the cnx loci plus another peptide, coded in the case of xanthine dehydrogenase I by the hx A locus, carrying the substrate binding site and specific for each enzyme. The synthesis of the cnx cofactor could be constitutive, whereas the synthesis of the hx B peptide is under two independent systems of control and each of the specific components under a specific system of control. It is proposed that control systems for both xanthine dehydrogenase I and II are of the positive type. In the Appendix the induction of xanthine dehydrogenase II in wild type and mutant strains is described. The isolation and preliminary characterisation of mutants lacking xanthine dehydrogenase II but not xanthine dehydrogenase I is reported. Some of the mutations are allelic with apl Ac mutanta, while another one identifies a new locus coding possibly for the substrate binding site of xanthine dehydrogenase II.