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Regio‐ and stereo‐selective oxidation of fluorinated substrates by recombinant cytochrome P450 BM3 variants
Author(s) -
Yu Steve S.F.,
Wu LiLan,
Chiang ChihHsiang,
Ramu Ravirala,
Yang ChungLing,
Ng Kok Yaoh,
Luo WenI,
Chan Sunney I.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1007.5
Subject(s) - chemistry , hydroxylation , cytochrome p450 , carboxylate , substituent , lauric acid , stereochemistry , substrate (aquarium) , heme , cytochrome , van der waals force , active site , catalysis , fatty acid , enzyme , organic chemistry , oceanography , molecule , geology
We recently showed that, upon the addition of fluorine substituents on n‐octane, van der Waals interactions including dispersion between a ‐CF 2 ‐ and an aromatic π system account for changes in the alkane hydroxylation mediated by variants of recombinant cytochrome P450 BM3. Here, for the first time, we demonstrate that P450 BM3 also recognizes fluorinated C 12 –C 15 chain‐length fatty acids. Despite the fact that residues, Arg47 and Tyr52, exert significant controls for the sub‐terminal hydroxylation via hydrogen bonding interactions at carboxylate ends of these fatty acids, in any case, the fluorine substituent(s) at omega position plays an essential role in the regio‐selective hydroxylation occurred at omega‐3 position through unique van der Waals interactions. For instance, the catalytic turnover of fluorinated lauric acid substrates by recombinant cytochrome P450 BM3 exhibit higher activities than that of their parent substrate. In conclusion, our data suggest that hydrophobic residues in the heme pocket of P450 enzymes are involved in tuning the orientation of substrates and this further leads to the controlled oxidation of aliphatics mediated by high valent iron‐oxo species. This work was supported by Academia Sinica and grants from the National Science Council, R.O.C. (NSC 97–2113‐M‐001–006‐MY3 and 101–2113‐M‐001–007‐MY3).