Sulfur metabolism is ubiquitous and terminally synthesizes various biomolecules that are crucial for organisms, such as
sulfur-containing
amino acids and co-factors,
sulfolipids and sulfated saccharides. Entamoeba histolytica, a protozoan parasite responsible for
amoebiasis, possesses the unique
sulfur metabolism features of atypical localization and its terminal product being limited to
sulfolipids. Here, we present an overall scheme of E. histolytica
sulfur metabolism by relating all
sulfotransferases and
sulfatases to their substrates and products. Furthermore, a novel
sulfur metabolite,
fatty alcohol disulfates, was identified and shown to play an important role in trophozoite proliferation.
Cholesteryl sulfate, another synthesized sulfolipid, was previously demonstrated to play an important role in encystation, a differentiation process from proliferative trophozoite to dormant
cyst. Entamoeba survives by alternating between these two distinct forms; therefore, Entamoeba
sulfur metabolism contributes to the parasitic life cycle via its terminal products. Interestingly, this unique feature of
sulfur metabolism is not conserved in the nonparasitic close relative of Entamoeba, Mastigamoeba, because lateral gene transfer-mediated acquisition of
sulfatases and
sulfotransferases, critical
enzymes conferring this feature, has only occurred in the Entamoeba lineage. Hence, our findings suggest that sulfolipid metabolism has a causal relationship with parasitism.