Enzymatic Synthesis of Bioinformatically Predicted Microcin C-Like Compounds Encoded by Diverse Bacteria

ABSTRACT The Trojan horse Escherichia coli antibiotic microcin C (McC) consists of a heptapeptide attached to adenosine through a phosphoramidate linkage. McC is synthesized by the MccB enzyme, which terminally adenylates the ribosomally synthesized heptapeptide precursor MccA. The peptide part is r...

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Autores principales:	Olga Bantysh, Marina Serebryakova, Kira S. Makarova, Svetlana Dubiley, Kirill A. Datsenko, Konstantin Severinov
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2014
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/2b3508d6d692455c823ee61a1d172080
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spelling	oai:doaj.org-article:2b3508d6d692455c823ee61a1d1720802021-11-15T15:47:38ZEnzymatic Synthesis of Bioinformatically Predicted Microcin C-Like Compounds Encoded by Diverse Bacteria10.1128/mBio.01059-142150-7511https://doaj.org/article/2b3508d6d692455c823ee61a1d1720802014-07-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01059-14https://doaj.org/toc/2150-7511ABSTRACT The Trojan horse Escherichia coli antibiotic microcin C (McC) consists of a heptapeptide attached to adenosine through a phosphoramidate linkage. McC is synthesized by the MccB enzyme, which terminally adenylates the ribosomally synthesized heptapeptide precursor MccA. The peptide part is responsible for McC uptake; it is degraded inside the cell to release a toxic nonhydrolyzable aspartyl-adenylate. Bionformatic analysis reveals that diverse bacterial genomes encoding mccB homologues also contain adjacent short open reading frames that may encode MccA-like adenylation substrates. Using chemically synthesized predicted peptide substrates and recombinant cognate MccB protein homologs, adenylated products were obtained in vitro for predicted MccA peptide-MccB enzyme pairs from Helicobacter pylori, Streptococcus thermophilus, Lactococcus johnsonii, Bartonella washoensis, Yersinia pseudotuberculosis, and Synechococcus sp. Some adenylated products were shown to inhibit the growth of E. coli by targeting aspartyl-tRNA synthetase, the target of McC. IMPORTANCE Our results prove that McC-like adenylated peptides are widespread and are encoded by both Gram-negative and Gram-positive bacteria and by cyanobacteria, opening ways for analyses of physiological functions of these compounds and for creation of microcin C-like antibiotics targeting various bacteria.Olga BantyshMarina SerebryakovaKira S. MakarovaSvetlana DubileyKirill A. DatsenkoKonstantin SeverinovAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 5, Iss 3 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Olga Bantysh Marina Serebryakova Kira S. Makarova Svetlana Dubiley Kirill A. Datsenko Konstantin Severinov Enzymatic Synthesis of Bioinformatically Predicted Microcin C-Like Compounds Encoded by Diverse Bacteria
description	ABSTRACT The Trojan horse Escherichia coli antibiotic microcin C (McC) consists of a heptapeptide attached to adenosine through a phosphoramidate linkage. McC is synthesized by the MccB enzyme, which terminally adenylates the ribosomally synthesized heptapeptide precursor MccA. The peptide part is responsible for McC uptake; it is degraded inside the cell to release a toxic nonhydrolyzable aspartyl-adenylate. Bionformatic analysis reveals that diverse bacterial genomes encoding mccB homologues also contain adjacent short open reading frames that may encode MccA-like adenylation substrates. Using chemically synthesized predicted peptide substrates and recombinant cognate MccB protein homologs, adenylated products were obtained in vitro for predicted MccA peptide-MccB enzyme pairs from Helicobacter pylori, Streptococcus thermophilus, Lactococcus johnsonii, Bartonella washoensis, Yersinia pseudotuberculosis, and Synechococcus sp. Some adenylated products were shown to inhibit the growth of E. coli by targeting aspartyl-tRNA synthetase, the target of McC. IMPORTANCE Our results prove that McC-like adenylated peptides are widespread and are encoded by both Gram-negative and Gram-positive bacteria and by cyanobacteria, opening ways for analyses of physiological functions of these compounds and for creation of microcin C-like antibiotics targeting various bacteria.
format	article
author	Olga Bantysh Marina Serebryakova Kira S. Makarova Svetlana Dubiley Kirill A. Datsenko Konstantin Severinov
author_facet	Olga Bantysh Marina Serebryakova Kira S. Makarova Svetlana Dubiley Kirill A. Datsenko Konstantin Severinov
author_sort	Olga Bantysh
title	Enzymatic Synthesis of Bioinformatically Predicted Microcin C-Like Compounds Encoded by Diverse Bacteria
title_short	Enzymatic Synthesis of Bioinformatically Predicted Microcin C-Like Compounds Encoded by Diverse Bacteria
title_full	Enzymatic Synthesis of Bioinformatically Predicted Microcin C-Like Compounds Encoded by Diverse Bacteria
title_fullStr	Enzymatic Synthesis of Bioinformatically Predicted Microcin C-Like Compounds Encoded by Diverse Bacteria
title_full_unstemmed	Enzymatic Synthesis of Bioinformatically Predicted Microcin C-Like Compounds Encoded by Diverse Bacteria
title_sort	enzymatic synthesis of bioinformatically predicted microcin c-like compounds encoded by diverse bacteria
publisher	American Society for Microbiology
publishDate	2014
url	https://doaj.org/article/2b3508d6d692455c823ee61a1d172080
work_keys_str_mv	AT olgabantysh enzymaticsynthesisofbioinformaticallypredictedmicrocinclikecompoundsencodedbydiversebacteria AT marinaserebryakova enzymaticsynthesisofbioinformaticallypredictedmicrocinclikecompoundsencodedbydiversebacteria AT kirasmakarova enzymaticsynthesisofbioinformaticallypredictedmicrocinclikecompoundsencodedbydiversebacteria AT svetlanadubiley enzymaticsynthesisofbioinformaticallypredictedmicrocinclikecompoundsencodedbydiversebacteria AT kirilladatsenko enzymaticsynthesisofbioinformaticallypredictedmicrocinclikecompoundsencodedbydiversebacteria AT konstantinseverinov enzymaticsynthesisofbioinformaticallypredictedmicrocinclikecompoundsencodedbydiversebacteria
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Enzymatic Synthesis of Bioinformatically Predicted Microcin C-Like Compounds Encoded by Diverse Bacteria

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