Department of Chemical Engineering, Texas A&M University, College Station, Texas 77843, United States.
Interdisciplinary Graduate Program in Genetics and Genomics, Texas A&M University, College Station, Texas 77843, United States.
ACS Chem Biol. 2022 Jul 15;17(7):1665-1671. doi: 10.1021/acschembio.2c00312. Epub 2022 Jun 10.
Human gastrointestinal microbiota are known for the keto-reductive metabolism of small-molecule pharmaceuticals; however, the responsible enzymes remain poorly understood. Through biochemical assays, we report the identification of enzymes encoded in the genome of that can reduce the ketone groups of nabumetone, hydrocortisone, and tacrolimus. The homologues to a newly identified enzyme (i.e., DesE) are potentially widely distributed in the gut microbiome. The selected enzymes display different levels of activities against additional chemicals such as two dietary compounds (i.e., raspberry ketone and zingerone), chemotherapeutic drug doxorubicin, and its aglycone metabolite doxorubicinone. Thus, our results expand the repertoire of enzymes that can reduce the ketone groups in small molecules and could serve as the basis for future personalized medicine approaches.
人体胃肠道微生物群以小分子药物的酮还原代谢而闻名；然而，负责的酶仍然知之甚少。通过生化分析，我们报告了在 的基因组中编码的可以还原酮洛芬、氢化可的松和他克莫司酮基团的酶的鉴定。新鉴定的酶（即 DesE）的同源物可能广泛分布于肠道微生物组中。所选的酶对其他化学物质（如两种膳食化合物（即树莓酮和姜酮）、化疗药物阿霉素及其糖苷元代谢物阿霉素酮）表现出不同水平的活性。因此，我们的结果扩展了可以还原小分子中酮基团的酶的种类，并且可以作为未来个体化药物治疗方法的基础。
