Comparative functional analysis of CYP71AV1 natural variants reveals an important residue for the successive oxidation of amorpha-4,11-diene

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• 作者：Aya Komori^a ; ^b ; ^d ; Munenori Suzuki^a ; ^d ; Hikaru Seki^a ; ^c ; ^d ; Tomoko Nishizawa^c ; Jacobus Johannes Marion Meyer^e ; Hideaki Shimizu^b ; Shigeyuki Yokoyama^b ; Toshiya Muranaka^a ; ^c ; ^d ; ^{muranaka@bio.eng.osaka-u.ac.jp}
• 关键词：abCYP71AV1 ; CYP71AV1 isolated from A. absinthium ; Aldh1 ; aldehyde dehydrogenase ; ADS ; amorpha-4 ; 11-diene synthase ; afCYP71AV1 ; CYP71AV1 isolated from A. afra ; CPR ; cytochrome P450 reductase ; Dbr2 ; artemisinic aldehyde ¦¤11(13) reductase ; FDP ; farnesyl dip
• 刊名：FEBS Letters
• 出版年：2013
• 出版时间：31 January, 2013
• 年：2013
• 卷：587
• 期：3
• 页码：278-284
• 全文大小：1214 K

文摘

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.