Peptide epimerase-dehydratase complex responsible for biosynthesis of the linaridin class ribosomal peptides


Xiao Wanlu1,Tsunoda Takeshi2ORCID,Maruyama Chitose3,Hamano Yoshimitsu3,Ogasawara Yasushi2ORCID,Dairi Tohru2ORCID


1. Graduate School of Chemical Sciences and Engineering, Hokkaido University , Sapporo, Hokkaido 060-8628 , Japan

2. Graduate School of Engineering, Hokkaido University , Sapporo, Hokkaido 060-8628 , Japan

3. Department of Bioscience, Fukui Prefectural University , Yoshida-Gun, Fukui , Japan


ABSTRACT Grisemycin, salinipeptin, and cypemycin belong to the linaridin class of ribosomally synthesized and posttranslationally modified peptides that contain multiple dehydrobutyrine and D-amino acid residues. The biosynthetic gene clusters of these linaridins lack obvious candidate genes for the dehydratase and epimerase required to introduce dehydrobutyrine and D-amino acid residues, respectively. However, we previously demonstrated that the grisemycin (grm) cluster contained cryptic dehydratase and epimerase genes by heterologous expression of this biosynthetic gene cluster in Streptomyces lividans and proposed that two genes (grmH and grmL) with unknown functions catalyze dehydration and epimerization reactions. In this study, we confirmed that both GrmH and GrmL, which were shown to constitute a protein complex by a co-purification experiment, were required to catalyze the dehydration, epimerization, and proteolytic cleavage of a precursor peptide GrmA by in vivo experiments. Furthermore, we demonstrated that GrmH/GrmL complex accepted salinipeptin and cypemycin precursor peptides, which possess three additional amino acids.


Grants-in-Aid for Scientific Research

Hokkaido University DX Doctoral Fellowship


Oxford University Press (OUP)


Organic Chemistry,Molecular Biology,Applied Microbiology and Biotechnology,General Medicine,Biochemistry,Analytical Chemistry,Biotechnology







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