An amitochondriate parasite, Entamoeba histolytica, has a bifunctional ADHE enzyme (EhADH2) that contains separate acetaldehyde (ALDH) and alcohol (ADH) dehydrogenase activities. In a cluster of 25 bifunctional enzymes of single cell eukaryotes and bacteria, we present a phylogenetic analysis that suggests a lateral gene transfer event (prokaryotic ancestor to single-cell eukaryotic ancestor) and a complex structure that aligns with key homologs in the ADHE evolutionary history based on their similarity with bacterial alcohol dehydrogenases. We show that the ADHE in Entamoeba lineage diverged independently but shows significant similarities to the structure of ADHE in Fusobacterium, and a complex model that maps its ALDH and ADH domain well with bacteria such as Geobaccillus thermoglucosidasius. Our analyses likely support a lateral acquisition of an EhADH2-like ancestral gene from bacteria. Analysis using several evolutionary analyses software programs reveal that the enzyme structure is highly conserved, and maintains a similar function within a diverse set of pathogens, including Escherichia coli and Clostridium spp.