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Transporter Protein-Guided Genome Mining for Head-to-Tail Cyclized Bacteriocins

Head-to-tail cyclized bacteriocins are ribosomally synthesized antimicrobial peptides that are defined by peptide backbone cyclization involving the N- and C- terminal amino acids. Their cyclic nature and overall three-dimensional fold confer superior stability against extreme pH and temperature con...

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Autores principales: Major, Daniel, Flanzbaum, Lara, Lussier, Leah, Davies, Carly, Caldo, Kristian Mark P., Acedo, Jeella Z.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8659200/
https://www.ncbi.nlm.nih.gov/pubmed/34885800
http://dx.doi.org/10.3390/molecules26237218
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author Major, Daniel
Flanzbaum, Lara
Lussier, Leah
Davies, Carly
Caldo, Kristian Mark P.
Acedo, Jeella Z.
author_facet Major, Daniel
Flanzbaum, Lara
Lussier, Leah
Davies, Carly
Caldo, Kristian Mark P.
Acedo, Jeella Z.
author_sort Major, Daniel
collection PubMed
description Head-to-tail cyclized bacteriocins are ribosomally synthesized antimicrobial peptides that are defined by peptide backbone cyclization involving the N- and C- terminal amino acids. Their cyclic nature and overall three-dimensional fold confer superior stability against extreme pH and temperature conditions, and protease degradation. Most of the characterized head-to-tail cyclized bacteriocins were discovered through a traditional approach that involved the screening of bacterial isolates for antimicrobial activity and subsequent isolation and characterization of the active molecule. In this study, we performed genome mining using transporter protein sequences associated with experimentally validated head-to-tail cyclized bacteriocins as driver sequences to search for novel bacteriocins. Biosynthetic gene cluster analysis was then performed to select the high probability functional gene clusters. A total of 387 producer strains that encode putative head-to-tail cyclized bacteriocins were identified. Sequence and phylogenetic analyses revealed that this class of bacteriocins is more diverse than previously thought. Furthermore, our genome mining strategy captured hits that were not identified in precursor-based bioprospecting, showcasing the utility of this approach to expanding the repertoire of head-to-tail cyclized bacteriocins. This work sets the stage for future isolation of novel head-to-tail cyclized bacteriocins to serve as possible alternatives to traditional antibiotics and potentially help address the increasing threat posed by resistant pathogens.
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spelling pubmed-86592002021-12-10 Transporter Protein-Guided Genome Mining for Head-to-Tail Cyclized Bacteriocins Major, Daniel Flanzbaum, Lara Lussier, Leah Davies, Carly Caldo, Kristian Mark P. Acedo, Jeella Z. Molecules Article Head-to-tail cyclized bacteriocins are ribosomally synthesized antimicrobial peptides that are defined by peptide backbone cyclization involving the N- and C- terminal amino acids. Their cyclic nature and overall three-dimensional fold confer superior stability against extreme pH and temperature conditions, and protease degradation. Most of the characterized head-to-tail cyclized bacteriocins were discovered through a traditional approach that involved the screening of bacterial isolates for antimicrobial activity and subsequent isolation and characterization of the active molecule. In this study, we performed genome mining using transporter protein sequences associated with experimentally validated head-to-tail cyclized bacteriocins as driver sequences to search for novel bacteriocins. Biosynthetic gene cluster analysis was then performed to select the high probability functional gene clusters. A total of 387 producer strains that encode putative head-to-tail cyclized bacteriocins were identified. Sequence and phylogenetic analyses revealed that this class of bacteriocins is more diverse than previously thought. Furthermore, our genome mining strategy captured hits that were not identified in precursor-based bioprospecting, showcasing the utility of this approach to expanding the repertoire of head-to-tail cyclized bacteriocins. This work sets the stage for future isolation of novel head-to-tail cyclized bacteriocins to serve as possible alternatives to traditional antibiotics and potentially help address the increasing threat posed by resistant pathogens. MDPI 2021-11-28 /pmc/articles/PMC8659200/ /pubmed/34885800 http://dx.doi.org/10.3390/molecules26237218 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Major, Daniel
Flanzbaum, Lara
Lussier, Leah
Davies, Carly
Caldo, Kristian Mark P.
Acedo, Jeella Z.
Transporter Protein-Guided Genome Mining for Head-to-Tail Cyclized Bacteriocins
title Transporter Protein-Guided Genome Mining for Head-to-Tail Cyclized Bacteriocins
title_full Transporter Protein-Guided Genome Mining for Head-to-Tail Cyclized Bacteriocins
title_fullStr Transporter Protein-Guided Genome Mining for Head-to-Tail Cyclized Bacteriocins
title_full_unstemmed Transporter Protein-Guided Genome Mining for Head-to-Tail Cyclized Bacteriocins
title_short Transporter Protein-Guided Genome Mining for Head-to-Tail Cyclized Bacteriocins
title_sort transporter protein-guided genome mining for head-to-tail cyclized bacteriocins
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8659200/
https://www.ncbi.nlm.nih.gov/pubmed/34885800
http://dx.doi.org/10.3390/molecules26237218
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