Budget Amount *help |
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2017: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2016: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2015: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
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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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