2017 Fiscal Year Final Research Report
Mechanistic Enzymology of Radical SAM Enzymes
| Project/Area Number |
15H03834
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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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| Research Field |
Bio-related chemistry
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| Research Institution | Tokyo Institute of Technology |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | ラジカルSAM酵素 / 生合成 / 反応機構 |
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| Outline of Final Research Achievements |
In this study, functional analysis of a radical S-adenosyl-L-methionine (SAM) dehydratase AprD4 and a methylcobalamin-dependent radical SAM methyltransferase Fom3 were performed.
A radical SAM dehydratase AprD4 and an NADPH-dependent reductase AprD3 are responsible for the C3′-deoxygenation of pseudodisaccharide paromamine in the biosynthesis of apramycin/tobramycin. AprD4 catalyzes the C3’-dehydration of paromamine via a radical-mediated reaction mechanism to give 4’-oxolividamine, which is then reduced by AprD3 with NADPH to afford lividamine. Further, the substrate specificity of this unique combination of enzymes has been investigated.
A methylcobalamin-dependent radical SAM methyltransferase Fom3 was found to catalyze the C-methylation of cytidylyl-2-hydroxyethylphosphonate to give cytidylyl-2-hydroxypropylphosphonate in the biosynthesis of a unique C-P bond containing antibiotic fosfomycin in Streptomyces.
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| Free Research Field |
天然物有機化学
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