Peptide synthesis cooperatively achieved by peptide ligase and ribosomes
Project/Area Number |
25560397
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Allocation Type | Multi-year Fund |
Research Field |
Biomolecular chemistry
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Research Institution | Hokkaido University |
Principal Investigator |
DAIRI Tohru 北海道大学, 工学(系)研究科(研究院), 教授 (70264679)
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Project Period (FY) |
2013-04-01 – 2015-03-31
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Project Status |
Completed (Fiscal Year 2014)
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Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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Keywords | フェガノマイシン / ペプチド抗生物質 / 放線菌 / ペプチドライゲース / ぺプチド抗生物質 / リボソーマルペプチド |
Outline of Final Research Achievements |
Pheganomycin (PGM) (1) consists of a nonproteinogenic amino acid, (S)-2-(3,5-dihydroxy-4-methoxyphenyl)-2-guanidinoacetic acid (2) at the N-terminus and a proteinogenic core peptide derived from NVKDGPT or NVKDR. The biosynthetic gene cluster was identified in Streptomyces cirratus to contain a gene encoding a precursor peptide, which included both the core peptides, and several genes plausibly encoding enzymes for 2 biosynthesis. We identified a gene (pgm1) responsible for the peptide bond formation between 2 and the peptides in the cluster. A pgm1-disruptant lost 1 productivity and recombinant PGM1 catalyzed the ATP-dependent peptide bond formation. This is the first example of cooperative peptide synthesis achieved by ribosome and peptide ligase using a peptide as a nucleophile. PGM1 accepted a variety of peptides as the nucleophile and the flexibility was comprehended by the crystal structure of PGM1 and the mutagenesis analyses.
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Report
(3 results)
Research Products
(18 results)
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[Journal Article] A peptide ligase and the ribosome cooperate to synthesize the peptide pheganomycin.2015
Author(s)
Noike, M., Matsui, T., Ooya, K., Sasaki, I., Ohtaki, S., Hamano, Y., Maruyama, C., Ishikawa, J., Satoh, Y., Ito, H., Morita, H. and Dairi T.
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Journal Title
Nature Chemical Biology
Volume: 11
Issue: 1
Pages: 71-76
DOI
NAID
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] リボソームと新規ペプチドライゲースによる協同的ペプチド生成機構2014
Author(s)
野池基義, 松井 崇, 雄谷洸一, 佐々木郁雄, 丸山千登勢, 濱野吉十, 石川 淳, 佐藤康治, 伊藤 肇, 森田洋行, 大利 徹
Organizer
第56回天然有機化合物討論会
Place of Presentation
高知県立県民文化ホール(高知県高知市)
Year and Date
2014-10-15 – 2014-10-27
Related Report
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