Elucidation of biosynthetic pathways towards tetrodotoxin and saxitoxin based on the structures of novel biosynthetic intermediates

2016 Fiscal Year Final Research Report

• Project/Area Number: 26292057
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Bioorganic chemistry
• Research Institution: Tohoku University
• Principal Investigator: Yamashita Mari 東北大学, (連合)農学研究科(研究院), 教授 (50192430)
• Co-Investigator(Renkei-kenkyūsha): NISHIKAWA TOSHIO 名古屋大学, 大学院生命農学研究科, 教授 (90208158) ; NAGASAWA KAZUO 東京農工大学, 大学院工学研究院, 教授 (10247223) ; KONOKI KEIICHI 東北大学, 大学院農学研究科, 准教授 (40292825) ; CHO YUKO 東北大学, 大学院農学研究科, 助教 (60323086)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: テトロドトキシン / サキシトキシン / 生合成 / LC/MS / 中間体 / グアニジン

Outline of Final Research Achievements

We reported the first C10-C5 directly bonded tetrodotoxin (TTX) analogues from newts, and proposed monoterpene origin of TTX. In this study, five novel bicyclic guanidine compounds related to TTX were isolated and their structures were determined. These structures strongly supported monoterpene origin of TTX.
Although biosynthetic genes corresponding to production of STX had been reported, chemical study of intermediates were not enough. In this study, Int-A', Int-C'2, and CyclicC' were chemically synthesized, and identified in toxin producing cyanobacterium and dinoflagellate using high resolution LC-MS/MS. In addition, incorporation experiments with 15N labeled these intermediates indicated that Int-A' and Int-C'2 are genuine precursors of STX analogues and Cyclic C' is a shunt compound. This is the first shunt pathway in STX biosynthesis ever found.

Free Research Field

天然物化学