Comprehensive elucidation of the biosynthetic pathway of arzanol to establish its microbial production platform
| Project/Area Number |
18K06715
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 47050:Environmental and natural pharmaceutical resources-related
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| Research Institution | University of Toyama |
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Principal Investigator |
Taura Futoshi 富山大学, 学術研究部薬学・和漢系, 准教授 (00301341)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | アルザノール / カレープラント / 生合成 / 二次代謝 / 薬用植物 / プレニル転移酵素 / 生物生産 |
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| Outline of Final Research Achievements |
In this project, I have attempted comprehensive understanding and elucidation of the biosynthetic genes of arzanol, a meroterpenoid with a potent anti-inflammatory activity isolated from a medicinal plant Helichrysum italicum. I have successfully cloned genes coding for a polyketide synthase named HiPKS1 and a prenyltransferase HiPT2, which are involved in arzanol biosynthetic pathway, and characterized their structural and biochemical properties. In addition, I established the heterologous expression system of each biosynthetic enzyme to develop the biotechnological production of arzanol. Although I have not identified the enzyme catalyzing the final step to synthesize arzanol, I made a considerable progress concerning arzanol biosynthesis leading to biological production of this invaluable natural product.
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| Academic Significance and Societal Importance of the Research Achievements |
カレープラントが産生する多様な二次代謝産物の中でも、アルザノールはNF-κBの活性化、TNF-αの放出、prostaglandin E2の生合成をいずれも阻害することで強力な抗炎症作用を発現するほか、T細胞でのHIV-1の複製阻害およびがん細胞に対する細胞毒性など種々有用な生物活性を示すことが報告されている。本研究ではアルザノールの生合成に関与するポリケチド合成酵素およびプレニル基転移酵素を初めて同定した。得られた各酵素はともにPichia pastorisでの大量発現が可能であり、重要天然物アルザノールの微生物生産に向けた基盤整備を行うことができたと考えている。
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Report
(4 results)
Research Products
(22 results)
