Efficient tryptophan-catabolizing activity is consistently conserved through evolution of TDO enzymes, but not IDO enzymes.

Abstract

Indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) enzymes have independently evolved to catalyze the first step in the catabolism of tryptophan (L-Trp) through the kynurenine pathway. TDO is found in almost all metazoan and many bacterial species, but not in fungi. We show that TDO enzymes have high catalytic-efficiency for L-Trp catabolism, regardless of their biological origin, suggesting that TDO has been an L-Trp-specific degrading enzyme throughout its evolution. Meanwhile, IDO was initially discovered in mammals, and subsequently has been found in lower vertebrates, several invertebrates, fungi and a number of bacterial species. Some lineages have independently generated multiple IDO paralogues through gene duplications. Interestingly, only mammalian IDO1s and fungal "typical" IDOs have high affinity and catalytic efficiency for L-Trp catabolism, comparable to TDOs. We show that invertebrate IDO enzymes have low affinity and catalytic efficiency for L-Trp catabolism. We suggest that the phylogenetic distribution of "low catalytic-efficiency IDOs" indicates the ancestral IDO also had low affinity and catalytic efficiency for L-Trp catabolism. IDOs with high catalytic-efficiency for L-Trp-catabolism may have evolved in certain lineages to fulfill particular biological roles. The low catalytic-efficiency IDOs have been well conserved in a number of lineages throughout their evolution, although it is not clear that the enzymes contribute significantly to L-Trp catabolism in these species. Investigation of other substrates and functions of the ancestral IDO and low catalytic efficiency IDOs may identify additional biological roles for these enzymes.