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Comparative functional analysis of CYP71AV1 natural variants reveals an important residue for the successive oxidation of amorpha‐4,11‐diene
Author(s) -
Komori Aya,
Suzuki Munenori,
Seki Hikaru,
Nishizawa Tomoko,
Meyer Jacobus Johannes Marion,
Shimizu Hideaki,
Yokoyama Shigeyuki,
Muranaka Toshiya
Publication year - 2013
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2012.11.031
Subject(s) - artemisinin , artemisia annua , residue (chemistry) , monooxygenase , biology , diene , stereochemistry , homology modeling , biochemistry , cytochrome p450 , chemistry , enzyme , plasmodium falciparum , organic chemistry , natural rubber , malaria , immunology
Artemisinin is an antimalarial sesquiterpenoid isolated from the aerial parts of the plant Artemisia annua . CYP71AV1, a cytochrome P450 monooxygenase was identified in the artemisinin biosynthetic pathway. CYP71AV1 catalyzes three successive oxidation steps at the C12 position of amorpha‐4,11‐diene to produce artemisinic acid. In this study, we isolated putative CYP71AV1 orthologs in different species of Artemisia . Comparative functional analysis of CYP71AV1 and its putative orthologs, together with homology modeling, enabled us to identify an amino acid residue (Ser479) critical for the second oxidation reaction catalyzed by CYP71AV1. Our results clearly show that a comparative study of natural variants is useful to investigate the structure–function relationships of CYP71AV1.