2021 Fiscal Year Final Research Report
Functional and structural analyses of complex-forming and activity-regulation mechanisms of the key enzymes in aspartate-pathway
| Project/Area Number |
18H02138
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 38030:Applied biochemistry-related
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| Research Institution | Kagawa University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Keywords | 超好熱菌 / アスパラギン酸キナーゼ / ホモセリン脱水素酵素 / アスパラギン酸経路 / Thermotoga maritima |
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| Outline of Final Research Achievements |
Aspartate kinase (AK) and homoserine dehydrogenase (HseDH) are involved in the biosynthetic pathway for L-threonine and L-lysine in plants and microorganisms. Both enzymes are important as potential targets for improving the nutritional value of food crops. AK and HseDH function as either a monofunctional enzyme or fused-bifunctional enzyme (AK-HseDH). These enzymes are highly regulated by the end products. However, information on the regulation mechanism remains limited because of their instability.
In the hyperthermophilic bacterium, Thermotoga maritima, we found presence of AK-HseDH and AK, both exhibit high stability. We revealed that the former to be an L-threonine-sensitive AK-HseDH, whose activity was not inhibited by L-lysine and the latter to be an L-lysine-sensitive AK, whose activity was not inhibited by L-threonine. Our results suggest that, in T. maritima, the AK-HseDH is related to the synthesis of L-threonine, whereas the AK functions in the synthesis of L-lysine.
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| Free Research Field |
構造生物学
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| Academic Significance and Societal Importance of the Research Achievements |
二機能型AK-HseDHおよび単一機能型AKはヒトを含む哺乳動物には存在しないため、病原微生物に対する抗菌薬開発の分子標的として注目される。また植物では、本経路の酵素反応によって上記必須アミノ酸含量が決まるため、酵素改変による食用作物や畜産飼料の栄養価改善が期待される。本研究では、T. maritimaの二機能型AK-HseDHと単一機能型AKを解析し、それぞれ従来と異なるタイプの調節機構を持ち、2つの酵素が役割分担をしていることが示唆された。このような例はこれまで知られておらず、新規な調節機構を提唱する点で学術的意義は大きい。また酵素改変による技術開発につながることが期待される。
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