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A peptide ligase and the ribosome cooperate to synthesize the peptide pheganomycin

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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)

Submitter: 大利 徹

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