| 研究課題/領域番号 |
18K06577
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| 研究機関 | 神戸大学 |
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研究代表者 |
ヴァヴリッカ クリストファー 神戸大学, 科学技術イノベーション研究科, 准教授 (20809199)
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| 研究分担者 |
清田 洋正 岡山大学, 環境生命科学研究科, 教授 (30234397)
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| 研究期間 (年度) |
2018-04-01 – 2021-03-31
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| キーワード | Bioproduction / Anti-virals / Sialic acid / Synthetic biology / Sulfonic acids / Fluorine |
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| 研究実績の概要 |
To speed up production of the medicinal chemistry targets, microbial systems to bioproduce target compounds were developed. Concepts for designing, building, testing and improving bioproduction systems were proven using alkaloid targets in a model study. The model alkaloid pathway is similar to our proposed sialic acid derivative synthesis in that decarboxylation is a key step, and also regarding key aldehyde intermediates. Therefore new aldehyde containing routes to the proposed sialic acid derivatives were explored using successful model reactions. Finally, a microbial system for 9-O-acetyl-sialic acid bioproduction was constructed. 9-O-acetylsialic acid is a potential probe or inhibitor of coronavirus, as well as a key intermediate of our proposed sialic acid derivatives.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
Regarding the original plan to produce fluorinated sialic acid derivatives as inhibitors of influenza, we have made progress in the introduction of fluroine into the C-1 position of open-chain analogs of our proposed compounds. In one model reaction, fluoromethy phenyl sulfone could undergo addition to a model aldehyde. In addition, we have made great progress in the development of next-generation methods for the production of valuable medicinal compounds. These synthetic biology methods for carrying out related reactions have already resulted in several high impact publications. Therefore we are confident that these new processes will continue to produce valuable targets relating to the proposed study.
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| 今後の研究の推進方策 |
We will continue to focus on two approaches to further develop our proposed fluorinated sialic acid analogs:
1) Production of open-chain analogs of fluorinated sialic acids. This will include an 8 carbon aldonic acid derived from oxidation of sialic acid. The open-chain analogs will be tested as inhibitors of influenza neuraminidase. Re-cyclization of the open-chain analogs may also be tested.
2) Microbial bioproduction of key intermediates using aldolase and O-acetyltransferase enzymes. Improvement of enzyme sequences will be carried out using protein structure modeling. In vivo production of target compounds will be tested in Escherichia coli. Comparison of the metabolism of fluorine labeled compounds vs natural compounds will be investigated.
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| 次年度使用額が生じた理由 |
Some of the ordered reagents and supplies were unable to be delivered by March. But these orders were able to be received in April. The research will be able to proceed without any problem.
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