Elucidation of the biosynthetic pathways of tetrodotoxin and saxitoxin based on the intermediates

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H03809
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Bioorganic chemistry
• Research Institution: Tohoku University
• Principal Investigator: Yamashita Mari 東北大学, 農学研究科, 教授 (50192430)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: テトロドトキシン / サキシトキシン / 生合成

Outline of Final Research Achievements

Seven novel bicyclic guanidino compounds were isolated from the tetrodotoxin (TTX) possessing pufferfish, and their structures were elucidated. These compounds have the same relative stereochemistry as that of TTX. Based on their structures, oxidative biosynthetic pathway towards TTX was suggested. For biosynthesis of saxitoxin (STX), predicted intermediates, 11-hydroxy Int-C’2 and Int-E’were chemically synthesized. They were identified in toxin producing dinoflagellate and cyanobacterium using HR-LC/MS. In addition, a new STX analogue, 12beta-deoxyGTX3 was identified in the toxic cyanobacterium using the standard which was prepared by chemical derivatization.

Free Research Field

天然物化学

Academic Significance and Societal Importance of the Research Achievements

フグ毒として知られるテトロドトキシン(TTX)は、最もよく知られた生物毒の一つであるが、その生合成機構は解明されていない。最近ではヨーロッパなどで食用の二枚貝などからもTTXが検出され、食品衛生上、その生合成機構を解明することは社会的にも重要である。また、麻痺性貝毒は近年猛威を振るっており、その代表的な毒素であるサキシトキシンの生合成は、世界各地で活発に研究されおり、その特異な三環性の化学構造から、生合成経路の解明は学術的にも注目を集めている。