Modulating the Coupling Efficiency of P450 BM3 by Controlling Water Diffusion through Access Tunnel Engineering

Abstract: Cytochromes P450 have gained much interest for their broad substrate scope in the catalysis of oxidation reactions for pharmaceuticals, plastics, and hormones. However, achieving high coupling efficiency by the engineering of P450s is still a big challenge. The presence of extra water around the active site is deemed to be related to uncoupling. In this study, the access tunnels of P450 BM3 from Bacillus megaterium are engineered to control water access from bulk solvent to the active site. Nine residues located in tunnels are investigated by site‐saturation mutagenesis to reduce water diffusion, thereby improving the coupling efficiency. The recombined variant N319L/T411V/T436A shows improved coupling efficiency (from 31.2 % to 52.6 %). Tunnel polarity analysis and molecular dynamics simulation further indicate that reduced water molecules around the active site lead to higher coupling efficiency. Overall, this study provides valuable insight on improving coupling efficiency by controlling water diffusion through tunnel engineering.

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch

References and Relationships

• Bibliographic citation: Modulating the Coupling Efficiency of P450 BM3 by Controlling Water Diffusion through Access Tunnel Engineering ; day:27 ; month:01 ; year:2022 ; extent:1 ; ChemSusChem ; (27.01.2022) (gesamt 1)

Contributors, Places and Time

• Creator: Meng, Shuaiqi ; Ji, Yu ; Liu, Luo ; Davari, Mehdi D. ; Schwaneberg, Ulrich

Further information

• DOI: 10.1002/cssc.202102434
• URN: urn:nbn:de:101:1-2022012714324310243339
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 15.08.2025, 7:21 AM CEST