Premium
Activity of human P450 2D6 in biphasic solvent systems
Author(s) -
Zhao Jin,
Tan Elaine,
Ferras Julian,
Auclair Karine
Publication year - 2007
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.21449
Subject(s) - cofactor , substrate (aquarium) , chemistry , solvent , hydrogen peroxide , redox , combinatorial chemistry , enzyme , organic synthesis , organic chemistry , catalysis , biology , ecology
Several limitations have restricted the use of P450 enzymes in synthesis, including the narrow substrate specificity of some P450 isoforms, the need for a redox partner and an expensive cofactor, incompatibility with organic solvents, and poor stability. We previously demonstrated that the natural redox partner and cofactor of the promiscuous P450s 3A4 and 2D6 can be efficiently substituted with some cheap hydrogen peroxide donors or organic peroxides. We report here that P450 2D6 maintains as much as 76% of its activity when used in buffer/organic emulsions. Product formation in biphasic solvent systems is comparable whether the natural redox partner and cofactor are used, or a surrogate. As reported for other enzymes, a correlation is observed between the log P and the suitability of a solvent for enzymatic activity. Moreover, the utility of our system was established by demonstrating the transformation of a novel hydrophobic substrate, not modified by P450 2D6 in the absence of organic solvent. Biotechnol. Bioeng. 2007;98; 508–513. © 2007 Wiley Periodicals, Inc.