Creation of novel P450 enzymes with high metabolizing activities toward polychlorinated biphenyls and modification of its intracellular localization

2014 Fiscal Year Final Research Report

• Project/Area Number: 25550064
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Modeling and technologies for environmental conservation and remediation
• Research Institution: Kobe University
• Principal Investigator: INUI Hideyuki 神戸大学, 遺伝子実験センター, 准教授 (90314509)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: ポリ塩化ビフェニル / P450 / 代謝

Outline of Final Research Achievements

Polychlorinated biphenyls (PCBs) show toxicity such as carcinogenicity through bioaccumulation because of its high lipophilicity and persistency. Identification of P450 monooxygenases metabolizing PCBs, creation of novel P450s with high metabolizing activities, and modification of intracellular localization of P450s were attempted to achieve remediation of PCBs in the environment.
One of PCB congeners, CB118 was metabolized by human CYP2B6 to hydroxylated metabolites due to proximity of the active center of P450s and CB118. Furthermore, P450 mutants contributed decrease of PCB toxicity, and P450s were localized in a plasma membrane.
These results showed that we established basic technologies on high metabolism of PCBs by creation of P450s with high metabolizing activities and localization of P450s.

Free Research Field

環境学