| Project/Area Number |
16K18692
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Bioorganic chemistry
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| Research Institution | Hokkaido University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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| Keywords | ペプチドリガーゼ / 酵素 / アミド結合 / 天然物 / 疑似ペプチド / 生合成 / 放線菌 / 二次代謝 / シュードペプチド / 抗生物質 |
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| Outline of Final Research Achievements |
We previously identified a novel amide bond forming enzyme (peptide ligase, PGM1) responsible for the biosynthesis of peptide antibiotic, pheganomycin. In this study, we studied PGM1 orthologs found in actinobacteria. We first analyzed a ortholog (KtmD) responsible for the biosynthesis of previously discovered novel pseudotripeptides, ketomemicins, which possess a C-terminal pseudodipeptide connected with a carbonylmethylene instead of an amide bond. We showed that KtmD was a novel dipeptide ligase catalyzing amide bond formation between amidino-arginine and pseudodipeptides in the final step of biosynthesis. We next examined the biosynthesis of pseudodipeptide structure in ketomemicins and fully characterized the biosynthetic pathway of the pseudodipeptide in vitro. Furthermore, we investigated other orthologs to probe the functions of these genes. We heterologously expressed ortholog-containing gene clusters in Streptomyces lividans and detected several specific metabolites.
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