The evolution of three types of indoleamine 2,3 dioxygenases in fungi with distinct molecular and biochemical characteristics

Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-degrading enzyme and known as a mammalian immunosuppressive molecule. In fungi, the primary role of IDO is to supply nicotinamide adenine dinucleotide (NAD(+)) via the kynurenine pathway. We previously reported that the koji-mold, Aspergillus oryzae has two IDO genes, IDO alpha and IDO beta. In the present study, we found that A. oryzae also has the third IDO, IDO gamma. These three-types of IDOs are widely distributed among the Pezizomycotina fungi, although the black truffle. Tuber melanosporum has only one corresponding gene to IDO alpha/IDO beta. The yeast, Saccharomyces cerevisiae has a single IDO gene. Generally, Pezizomycotina IDO alpha showed similar enzymatic properties to the yeast IDO, suggesting that the IDO alpha is a functional homologue of the S. cerevisiae IDO. In contrast to IDO alpha, the K-m value of IDO beta is higher. However, the reaction velocity of IDO beta is very fast, resulting in comparable or higher catalytic efficiency than IDO alpha. Thus IDO beta may functionally substitute for IDO alpha in fungal L-Trp metabolism. The enzymatic activity of IDO gamma was comparatively very low with the values of enzymatic parameters comparable to vertebrate IDO2 enzymes. IDO alpha and IDO beta have similar gene structures, suggesting that they were generated by gene duplication which occurred rather early in Pezizomycotina evolution, although the timing of the duplication remains debatable. In contrast, the phylogenetic trees suggest that IDO gamma s form an evolutionarily distinct group of IDO enzymes, with a closer relationship to group I bacterial IDOs than other fungal IDOs. The ancestor of the IDO gamma family is likely to have diverged from other eukaryotic IDOs at a very early stage of eukaryotic evolution. (c) 2012 Elsevier B.V. All rights reserved.