Laboratory of Biochemistry, Department of Applied Science, Faculty of Science, National University Corporation Kochi University, Kochi 780-8520, Japan.
J Mol Evol. 2011 Feb;72(2):160-8. doi: 10.1007/s00239-010-9412-5. Epub 2010 Dec 18.
Indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) are tryptophan-degrading enzymes. Mammalian IDO expression is induced by cytokines and has antimicrobial and immunomodulatory effects. A major role of mammalian TDO is to supply nicotinamide adenine dinucleotide (NAD(+)). In fungi, the IDO homologue is thought to be expressed constitutively and supply NAD(+), as TDO is absent from their genomes. Here, we reveal the distribution of IDO genes among fungal species and characterize their enzymatic activity. The yeast, Saccharomyces cerevisiae has only one IDO gene, whereas the koji-mold, Aspergillus oryzae has two genes, IDOα and IDOβ. The A. oryzae IDOα showed more similar enzymatic properties to those of S. cerevisiae IDO than IDOβ, suggesting that the A. oryzae IDOα is a functional homologue of the S. cerevisiae IDO. From the IDOβ gene, two isoforms, IDOβ and IDOβ(+) could be generated by alternative splicing. The latter contained a 17 amino acids insertion which were encoded by the first intron of IDOβ gene. In comparison to IDOβ(+), bacterially expressed IDOβ showed much lower K(m) value and more than five-times faster V(max) value, resulting in 85 times higher catalytic efficiency; i.e., the removal of the domain encoded by the first intron from IDOβ(+) increases its enzymatic activity drastically. This might be a unique regulation mechanism of the L-Trp metabolism in the A. oryzae. The levo-1-methyl tryptophan (L-1MT) is a good inhibitor of both IDO1 and IDO2. However, the activity of fungal IDOs tested was not inhibited at all by L-1MT.
吲哚胺 2,3-双加氧酶（IDO）和色氨酸 2,3-双加氧酶（TDO）是分解色氨酸的酶。哺乳动物 IDO 的表达受细胞因子诱导，具有抗微生物和免疫调节作用。哺乳动物 TDO 的主要作用是提供烟酰胺腺嘌呤二核苷酸（NAD(+)）。在真菌中，IDO 同源物被认为是组成性表达的，并提供 NAD(+)，因为 TDO 不存在于它们的基因组中。在这里，我们揭示了 IDO 基因在真菌物种中的分布，并对其酶活性进行了表征。酵母酿酒酵母只有一个 IDO 基因，而米曲霉有两个基因，IDOα和 IDOβ。与 IDOβ 相比，A. oryzae IDOα 的酶学特性更类似于 S. cerevisiae IDO，表明 A. oryzae IDOα 是 S. cerevisiae IDO 的功能同源物。从 IDOβ 基因中，可以通过选择性剪接产生两种同工酶，IDOβ 和 IDOβ(+)。后者包含由 IDOβ 基因的第一个内含子编码的 17 个氨基酸插入。与 IDOβ(+)相比，细菌表达的 IDOβ 表现出低得多的 K(m)值和快 5 倍以上的 V(max)值，导致催化效率提高 85 倍；即，从 IDOβ(+)中去除由第一个内含子编码的结构域极大地增加了其酶活性。这可能是米曲霉中 L-Trp 代谢的独特调控机制。L-1-甲基色氨酸（L-1MT）是 IDO1 和 IDO2 的良好抑制剂。然而，测试的真菌 IDO 的活性根本不受 L-1MT 的抑制。
