Chlamydiae contain homologs of TrpA (tryptophan synthase alpha chain), TrpB(tryptophan synthase beta chain) and TrpF (phosphoribosylanthranilate isomerase), as well as TrpR, the trptophan repressor.

BLAST searches with other bacterial trpE/G, trpD, and trpC sequences against both the chlamydia proteome and the chlamydia genome (translated) have not revealed evidence of these sequences, thus a more intensive search was conducted for them. Multiple protein alignments were constructed for each of the four missing enzymes, which in turn were used to generate hidden Markov models. These models produced no significant hits when used to search all open reading frames greater than 80 amino acids (ctd3pro.frames).

There are several possible explanations. One is that chlamydia trachomatis may not be capable of synthesizing tryptophan therefore require host cell supplementation. Second, functional homologs of TrpC, TrpD, TrpE/G are present, but the level of homology is too low to be recognized by current analysis. It is also possible that "new" enzymes that have not yet been characterized catalyze these reactions in chlamydiae.

Based on our Blast study against the Chlamydia muridarum and Chlamydia pneumoniae and Chlamydia trachomatis MOPN indicates that except Chlamydia trachomatis MOPN has trpF homolog, nono of other tryptophan biosynthesis genes present in C.trachomatis serovar D have been found in other Chlamydia species. However the Chlamydia pneumoniae appear to have a eukaryota-type aromatic amino acid (tryptophan) hydroxylase.

Since chlamydia has 3 out of the 7 genes in the tryptophan biosynthesis pathway, and the predicted function of CT0018 is that of a tryptophan operon repressor, this could suggest the presence of yet unidentified members of the pathway in the chlamydia genome. An alternative hypothesis is that remnants of a once intact tryptophan biosynthetic pathway have been recruited to serve other pathways. Or C.trachomatis serovar D might really don't have the tryptophan biosynthesis pathway and this species is in the evolution process of losing tryptophan pathway.