Mode-of-action and evolution of methylenedioxy bridge forming P450s in plant specialized metabolism

• Noguchi Akio

  Research Institute, Suntory Global Innovation Center Ltd.

• Horikawa Manabu

  Bioorganic Research Institute, Suntory Foundation for Life Sciences

• Murata Jun

  Bioorganic Research Institute, Suntory Foundation for Life Sciences

• Tera Masayuki

  Bioorganic Research Institute, Suntory Foundation for Life Sciences

• Kawai Yosuke

  Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University

• Ishiguro Masaji

  Niigata University of Pharmacy and Applied Life Sciences

• Umezawa Toshiaki

  Research Institute for Sustainable Humanosphere, Kyoto University

• Mizutani Masaharu

  Graduate School of Agricultural Science, Kobe University

• Ono Eiichiro

  Research Institute, Suntory Global Innovation Center Ltd.

抄録

(+)-Sesamin is a major furofran-class lignan in sesame seeds and harbors characteristic two methylenedioxy bridges (MDB) that are sequentially formed from (+)-pinoresinol via (+)-piperitol by a Sesamum indicum P450, CYP81Q1. However, the molecular basis for this unique catalytic activity of CYP81Q1 has been poorly understood. To elucidate MDB formation, we tested various natural and non-natural metabolites as substrates for CYP81Q1. A synthetic (+)-SC1mr and a naturally occurring (+)-kobusin showed inhibitory effect on the production of (+)-sesamin by CYP81Q1 unlike (+)-epipinoresinol and (−)-pinoresinol, indicating the strict diastereomer and enantiomer selectivity. Homology modeling followed by site-directed mutagenesis of CYP81Q1 showed that an amino acid residue crucial for MDB formation is a unique Ala residue (A308), located in I-helix proximal to the substrate pocket, responsible to the conserved distal-Thr residue. MDB by CYP81Q1 is produced possibly through the formation of a substrate-participated hydrogen-bonding network, since single replacement of the Ala by Thr severely and specifically lowered the MDB forming activity. This hypothesis is supported by a newly identified MDB-forming enzyme CYP81Q38 from Phryma leptostachya harboring an Ala responsible to Ala308 in CYP81Q1. An evolutional perspective of CYP81Q1 is discussed in relation to another MDB-forming CYP719As functionally conserved in Ranunculales.

収録刊行物

• Ｐｌａｎｔ　Ｂｉｏｔｅｃｈｎｏｌｏｇｙ

  Ｐｌａｎｔ　Ｂｉｏｔｅｃｈｎｏｌｏｇｙ 31 (5), 493-503, 2014

  日本植物バイオテクノロジー学会

キーワード

• P450
• lignan
• methylenedioxy bridge
• lamiales
• convergent evolution

詳細情報

• CRID: 1390282679303325056
• NII論文ID: 130004721162
• NII書誌ID: AA11250821
• DOI: 10.5511/plantbiotechnology.14.0828a
• ISSN: 13476114
• ISSN: 13424580
• NDL書誌ID: 026092028
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I026092028
• 本文言語コード: en
• データソース種別:
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  • NDL
  • Crossref
  • CiNii Articles
  • KAKEN
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