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Phage display and selection of lanthipeptides on the carboxy-terminus of the gene-3 minor coat protein.


ABSTRACT: Ribosomally synthesized and post-translationally modified peptides (RiPPs) are an emerging class of natural products with drug-like properties. To fully exploit the potential of RiPPs as peptide drug candidates, tools for their systematic engineering are required. Here we report the engineering of lanthipeptides, a subclass of RiPPs characterized by multiple thioether cycles that are enzymatically introduced in a regio- and stereospecific manner, by phage display. This was achieved by heterologous co-expression of linear lanthipeptide precursors fused to the widely neglected C-terminus of the bacteriophage M13 minor coat protein pIII, rather than the conventionally used N-terminus, along with the modifying enzymes from distantly related bacteria. We observe that C-terminal precursor peptide fusions to pIII are enzymatically modified in the cytoplasm of the producing cell and subsequently displayed as mature cyclic peptides on the phage surface. Biopanning of large C-terminal display libraries readily identifies artificial lanthipeptide ligands specific to urokinase plasminogen activator (uPA) and streptavidin.

SUBMITTER: Urban JH 

PROVIDER: S-EPMC5686179 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Phage display and selection of lanthipeptides on the carboxy-terminus of the gene-3 minor coat protein.

Urban Johannes H JH   Moosmeier Markus A MA   Aumüller Tobias T   Thein Marcus M   Bosma Tjibbe T   Rink Rick R   Groth Katharina K   Zulley Moritz M   Siegers Katja K   Tissot Kathrin K   Moll Gert N GN   Prassler Josef J  

Nature communications 20171115 1


Ribosomally synthesized and post-translationally modified peptides (RiPPs) are an emerging class of natural products with drug-like properties. To fully exploit the potential of RiPPs as peptide drug candidates, tools for their systematic engineering are required. Here we report the engineering of lanthipeptides, a subclass of RiPPs characterized by multiple thioether cycles that are enzymatically introduced in a regio- and stereospecific manner, by phage display. This was achieved by heterologo  ...[more]

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