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Hokkaido University Collection of Scholarly and Academic Papers >
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A peptide ligase and the ribosome cooperate to synthesize the peptide pheganomycin
| Title: | A peptide ligase and the ribosome cooperate to synthesize the peptide pheganomycin |
| Authors: | Noike, Motoyoshi Browse this author | | Matsui, Takashi Browse this author | | Ooya, Koichi Browse this author | | Sasaki, Ikuo Browse this author | | Ohtaki, Shouta Browse this author | | Hamano, Yoshimitsu Browse this author | | Maruyama, Chitose Browse this author | | Ishikawa, Jun Browse this author | | Satoh, Yasuharu Browse this author →KAKEN DB | | Ito, Hajime Browse this author →KAKEN DB | | Morita, Hiroyuki Browse this author | | Dairi, Tohru Browse this author →KAKEN DB |
| Issue Date: | Jan-2015 |
| Publisher: | Nature Publishing Group |
| Journal Title: | Nature chemical biology |
| Volume: | 11 |
| Issue: | 1 |
| Start Page: | 71 |
| End Page: | 76 |
| Publisher DOI: | 10.1038/nchembio.1697 |
| PMID: | 25402768 |
| Abstract: | Peptide antibiotics are typically biosynthesized by one of two distinct machineries in a ribosome-dependent or ribosome-independent manner. Pheganomycin (PGM (1)) and related analogs consist of the nonproteinogenic amino acid (S)-2-(3,5-dihydroxy-4-hydroxymethyl)phenyl-2-guanidinoacetic acid (2) and a proteinogenic core peptide, making their origin uncertain. We report the identification of the biosynthetic gene cluster from Streptomyces cirratus responsible for PGM production. Unexpectedly, the cluster contains a gene encoding multiple precursor peptides along with several genes plausibly encoding enzymes for the synthesis of amino acid 2. We identified PGM1, which has an ATP-grasp domain, as potentially capable of linking the precursor peptides with 2, and validate this hypothesis using deletion mutants and in vitro reconstitution. We document PGM1's substrate permissivity, which could be rationalized by a large binding pocket as confirmed via structural and mutagenesis experiments. This is to our knowledge the first example of cooperative peptide synthesis achieved by ribosomes and peptide ligases using a peptide nucleophile. |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/59457 |
| Appears in Collections: | 工学院・工学研究院 (Graduate School of Engineering / Faculty of Engineering) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 大利 徹
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