Abstract
S-[(Z)-2-aminovinyl]-d-cysteine (AviCys) is a unique motif found in several classes of ribosomally synthesized and post-translationally modified peptides (RiPPs). Biosynthesis of AviCys requires flavin-dependent Cys decarboxylases, which are highly divergent among different RiPP classes. In this study, we solved the crystal structure of the cypemycin decarboxylase CypD. We show that CypD is structurally highly similar to lanthipeptide decarboxylases despite the absence of sequence similarities between them. We further show that Cys decarboxylases from four RiPP classes have evolved independently and form two major clusters. These results reveal the convergent evolution of AviCys biosynthesis and suggest that all the flavin-dependent Cys decarboxylases likely have a similar Rossmann fold despite their sequence divergences.
Keywords:
HFCD; RiPP; decarboxylase; enzyme evolution; natural product biosynthesis.
© 2019 Federation of European Biochemical Societies.
Publication types
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Letter
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Research Support, Non-U.S. Gov't
MeSH terms
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Actinobacteria / classification
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Actinobacteria / enzymology*
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Actinobacteria / genetics
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Amino Acid Sequence
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Bacterial Proteins / chemistry*
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Bacterial Proteins / genetics
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Bacterial Proteins / metabolism
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Bacteriocins / biosynthesis
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Bacteriocins / chemistry
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Binding Sites
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Carboxy-Lyases / chemistry*
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Carboxy-Lyases / genetics
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Carboxy-Lyases / metabolism
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Cloning, Molecular
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Crystallography, X-Ray
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Cyanobacteria / classification
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Cyanobacteria / enzymology*
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Cyanobacteria / genetics
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Cysteine / analogs & derivatives*
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Cysteine / metabolism
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Escherichia coli / enzymology
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Escherichia coli / genetics
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Evolution, Molecular
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Firmicutes / classification
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Firmicutes / enzymology*
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Firmicutes / genetics
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Gene Expression
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Genetic Vectors / chemistry
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Genetic Vectors / metabolism
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Models, Molecular
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Phylogeny
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Protein Binding
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Protein Conformation, alpha-Helical
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Protein Conformation, beta-Strand
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Protein Interaction Domains and Motifs
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Sequence Alignment
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Structural Homology, Protein
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Substrate Specificity
Substances
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Bacterial Proteins
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Bacteriocins
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Recombinant Proteins
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cypemycin
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Carboxy-Lyases
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cysteine decarboxylase
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Cysteine