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

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• 作者：Hajime J. Yuasa^a ; ^{julie@kochi-u.ac.jp} ; Helen J. Ball^b
• 关键词：IDO ; indoleamine 2 ; 3-dioxygenase ; Kyn ; kynurenine ; 1-MT ; 1-methyl-tryptophan ; TDO ; tryptophan 2 ; 3-dioxygenase ; TON ; turnover number
• 刊名：Gene
• 出版年：2012
• 期刊代码：73_03781119
• 类别：bio
• 出版时间：1 August, 2012
• 卷：504
• 期：1
• 页码：64-74
• 文件大小：2530 K

摘要

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伪 and IDO尾. In the present study, we found that A. oryzae also has the third IDO, IDO纬. 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伪/IDO尾. The yeast, Saccharomyces cerevisiae has a single IDO gene. Generally, Pezizomycotina IDO伪 showed similar enzymatic properties to the yeast IDO, suggesting that the IDO伪 is a functional homologue of the S. cerevisiae IDO. In contrast to IDO伪, the K_m value of IDO尾 is higher. However, the reaction velocity of IDO尾 is very fast, resulting in comparable or higher catalytic efficiency than IDO伪. Thus IDO尾 may functionally substitute for IDO伪 in fungal L-Trp metabolism. The enzymatic activity of IDO纬 was comparatively very low with the values of enzymatic parameters comparable to vertebrate IDO2 enzymes. IDO伪 and IDO尾 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纬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纬 family is likely to have diverged from other eukaryotic IDOs at a very early stage of eukaryotic evolution.