Laboratory of Biochemistry, Department of Applied Science, National University Corporation Kochi University, Japan.
Gene. 2011 Oct 1;485(1):22-31. doi: 10.1016/j.gene.2011.06.002. Epub 2011 Jun 12.
Indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) are tryptophan-degrading enzymes that catalyze the first step in L-Trp catabolism via the kynurenine pathway. In mammals, TDO is mainly expressed in the liver and primarily supplies nicotinamide adenine dinucleotide (NAD(+)). TDO is widely distributed from mammals to bacteria. Active IDO enzymes have been reported only in vertebrates and fungi. In mammals, IDO activity plays a significant role in the immune system while in fungal species, IDO is constitutively expressed and supplies NAD(+), like mammalian TDO. A search of genomic databases reveals that some bacterial species also have a putative IDO gene. A phylogenetic analysis clustered bacterial IDOs into two groups, group I or group II bacterial IDOs. The catalytic efficiencies of group I bacterial IDOs were very low and they are suspected not to contribute significantly to L-Trp metabolism. The bacterial species bearing the group I bacterial IDO are scattered across a few phyla and no phylogenetically close relationship is observed between them. This suggests that the group I bacterial IDOs might be acquired by horizontal gene transmission that occurred in each lineage independently. In contrast, group II bacterial IDOs showed rather high catalytic efficiency. Particularly, the enzymatic characteristics (K(m), V(max) and inhibitor selectivity) of the Gemmatimonas aurantiaca IDO are comparable to those of mammalian IDO1, although comparison of the IDO sequences does not suggest a close evolutionary relationship. In several bacteria, TDO and the kynureninase gene (kynU) are clustered on their chromosome suggesting that these genes could be transcribed in an operon. Interestingly, G. aurantiaca has no TDO, and the IDO is clustered with kynU on its chromosome. Although the G. aurantiaca also has NadA and NadB to synthesize a quinolinic acid (a precursor of NAD(+)) via the aspartate pathway, the high activity of the G. aurantiaca IDO flanking the kynU gene suggests its IDO has a function similar to eukaryotic enzymes.
色氨酸 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，可通过犬尿氨酸途径催化 L-Trp 分解代谢的第一步。在哺乳动物中，TDO 主要在肝脏中表达，主要提供烟酰胺腺嘌呤二核苷酸 (NAD(+))。TDO 广泛分布于哺乳动物到细菌。已报道具有活性的 IDO 酶仅存在于脊椎动物和真菌中。在哺乳动物中，IDO 活性在免疫系统中发挥重要作用，而在真菌物种中，IDO 像哺乳动物 TDO 一样组成型表达并提供 NAD(+)。对基因组数据库的搜索显示，一些细菌物种也具有推定的 IDO 基因。系统发育分析将细菌 IDO 聚类为两组，即 I 组或 II 组细菌 IDO。I 组细菌 IDO 的催化效率非常低，怀疑它们对 L-Trp 代谢没有重要贡献。携带 I 组细菌 IDO 的细菌物种分散在几个门中，彼此之间没有观察到系统发育上的密切关系。这表明 I 组细菌 IDO 可能是通过独立发生在每个谱系中的水平基因转移获得的。相比之下，II 组细菌 IDO 表现出相当高的催化效率。特别是，黄单胞菌属的酶学特性 (K(m)、V(max)和抑制剂选择性)与哺乳动物 IDO1 相当，尽管 IDO 序列的比较并不表明它们之间存在密切的进化关系。在几种细菌中，TDO 和犬尿氨酸酶基因 (kynU) 都在其染色体上聚集，表明这些基因可以在操纵子中转录。有趣的是，黄单胞菌属没有 TDO，IDO 与 kynU 在其染色体上聚集。尽管黄单胞菌属也有 NadA 和 NadB 通过天冬氨酸途径合成喹啉酸（NAD(+) 的前体），但其侧翼有 kynU 基因的高活性 IDO 表明其 IDO 具有类似于真核酶的功能。
