2023 Fiscal Year Final Research Report
Researches on arseno-organic secondary metabolites produced by actinobacteria
| Project/Area Number |
22K20566
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund |
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| Review Section |
0601:Agricultural chemistry and related fields
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| Research Institution | Gakushuin University (2023)
The University of Tokyo (2022) |
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Principal Investigator |
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| Project Period (FY) |
2022-08-31 – 2024-03-31
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| Keywords | 有機ヒ素天然物 / 放線菌 / 二次代謝 / 生合成 / 単離構造決定 |
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| Outline of Final Research Achievements |
In this research, we initially attempted to elucidate the chemical structure of a structurally unknown organoarsenic metabolite (named bisenarsan) produced by Streptomyces lividans 66 (actinomycetes). Based on the preliminary structural analysis against trace purified material, we predicted the biosynthetic intermediate of bisenarsan and chemically synthesized it. By feeding the predicted biosynthetic intermediate into the culture medium, the production level of bisenarsan was significantly improved, enabling us to perform detailed structural analysis of bisenarsan and determine its chemical structure.
We also carried out gene disruption and genetic complementation of two enzyme genes and showed that they are involved in bisenarsan biosynthesis. These genes have previously been proposed to be implicated in bisenarsan biosynthesis and are widely distributed in the genomes of other actinomycetes.
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| Free Research Field |
天然物化学
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| Academic Significance and Societal Importance of the Research Achievements |
近年、微生物二次代謝によって生産される有機ヒ素化合物に優れた生理活性が見出された一方で、微生物ヒ素二次代謝に関する知見は依然乏しかった。本研究で化学構造が解明されたbisenarsanは放線菌二次代謝産物として同定された初の有機ヒ素化合物であった。すなわち、生理活性天然物の主要な生産者である放線菌において、ヒ素二次代謝経路の存在を実験的に立証された点で本研究は大きな学術的意義を持つ。
また、本研究でbisenarsan生合成への関与が立証された酵素遺伝子は他の放線菌ゲノムにも広く分布する事から、今後多様な代謝経路によって様々な生理活性を備えた有機ヒ素天然物の獲得に繋がることが期待される。
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