Human xenobiotic metabolism proteins have full-length and split homologs in the gut microbiome.

Abstract

We develop a pipeline to systematically find human proteins with gut microbial homologs, including those split across multiple microbial genes (e.g., operons). This reveals thousands of proteins with full-length gut homologs, especially reductases and hydrolases that metabolize xenobiotics. Nearly two dozen split homologs are also observed for central metabolic enzymes, many of which can transform substrate analogs; in two cases, previous studies verify that microbial split homologs enable the expected drug to be metabolized in vivo . These results, which we provide as a resource, map out homology and shed light on parallel drug metabolism between host and microbiome.