Directed evolution of enzymatic silicon-carbon bond cleavage in siloxanes

• 成果类型: Article
• 署名作者: Sarai, Nicholas S.; Fulton, Tyler J.; O'Meara, Ryen L.; Johnston, Kadina E.; Brinkmann-Chen, Sabine; Maar, Ryan R.; Tecklenburg, Ron E.; Roberts, John M.; Reddel, Jordan C. T.; Katsoulis, Dimitris E.; Arnold, Frances H.
• 署名单位: California Institute of Technology; California Institute of Technology; Merck & Company
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-10805
• DOI: 10.1126/science.adi5554
• 发表日期: 2024-01-26
• 页码: 438-443
• 关键词: volatile methyl siloxanes; octamethylcyclotetrasiloxane; cytochrome-p450; metabolites; kinetics

摘要

Volatile methylsiloxanes (VMS) are man-made, nonbiodegradable chemicals produced at a megaton-per-year scale, which leads to concern over their potential for environmental persistence, long-range transport, and bioaccumulation. We used directed evolution to engineer a variant of bacterial cytochrome P450BM3 to break silicon-carbon bonds in linear and cyclic VMS. To accomplish silicon-carbon bond cleavage, the enzyme catalyzes two tandem oxidations of a siloxane methyl group, which is followed by putative [1,2]-Brook rearrangement and hydrolysis. Discovery of this so-called siloxane oxidase opens possibilities for the eventual biodegradation of VMS.