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Use of Permanent Wall-Deficient Cells as a System for the Discovery of New-to-Nature Metabolites

Filamentous actinobacteria are widely used as microbial cell factories to produce valuable secondary metabolites, including the vast majority of clinically relevant antimicrobial compounds. Secondary metabolites are typically encoded by large biosynthetic gene clusters, which allow for a modular app...

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Autores principales: Shitut, Shraddha, Bergman, Güniz Özer, Kros, Alexander, Rozen, Daniel E., Claessen, Dennis
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760116/
https://www.ncbi.nlm.nih.gov/pubmed/33265975
http://dx.doi.org/10.3390/microorganisms8121897
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author Shitut, Shraddha
Bergman, Güniz Özer
Kros, Alexander
Rozen, Daniel E.
Claessen, Dennis
author_facet Shitut, Shraddha
Bergman, Güniz Özer
Kros, Alexander
Rozen, Daniel E.
Claessen, Dennis
author_sort Shitut, Shraddha
collection PubMed
description Filamentous actinobacteria are widely used as microbial cell factories to produce valuable secondary metabolites, including the vast majority of clinically relevant antimicrobial compounds. Secondary metabolites are typically encoded by large biosynthetic gene clusters, which allow for a modular approach to generating diverse compounds through recombination. Protoplast fusion is a popular method for whole genome recombination that uses fusion of cells that are transiently wall-deficient. This process has been applied for both inter- and intraspecies recombination. An important limiting step in obtaining diverse recombinants from fused protoplasts is regeneration of the cell wall, because this forces the chromosomes from different parental lines to segregate, thereby preventing further recombination. Recently, several labs have gained insight into wall-deficient bacteria that have the ability to proliferate without their cell wall, known as L-forms. Unlike protoplasts, L-forms can stably maintain multiple chromosomes over many division cycles. Fusion of such L-forms would potentially allow cells to express genes from both parental genomes while also extending the time for recombination, both of which can contribute to an increased chemical diversity. Here, we present a perspective on how L-form fusion has the potential to become a platform for novel compound discovery and may thus help to overcome the antibiotic discovery void.
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spelling pubmed-77601162020-12-26 Use of Permanent Wall-Deficient Cells as a System for the Discovery of New-to-Nature Metabolites Shitut, Shraddha Bergman, Güniz Özer Kros, Alexander Rozen, Daniel E. Claessen, Dennis Microorganisms Perspective Filamentous actinobacteria are widely used as microbial cell factories to produce valuable secondary metabolites, including the vast majority of clinically relevant antimicrobial compounds. Secondary metabolites are typically encoded by large biosynthetic gene clusters, which allow for a modular approach to generating diverse compounds through recombination. Protoplast fusion is a popular method for whole genome recombination that uses fusion of cells that are transiently wall-deficient. This process has been applied for both inter- and intraspecies recombination. An important limiting step in obtaining diverse recombinants from fused protoplasts is regeneration of the cell wall, because this forces the chromosomes from different parental lines to segregate, thereby preventing further recombination. Recently, several labs have gained insight into wall-deficient bacteria that have the ability to proliferate without their cell wall, known as L-forms. Unlike protoplasts, L-forms can stably maintain multiple chromosomes over many division cycles. Fusion of such L-forms would potentially allow cells to express genes from both parental genomes while also extending the time for recombination, both of which can contribute to an increased chemical diversity. Here, we present a perspective on how L-form fusion has the potential to become a platform for novel compound discovery and may thus help to overcome the antibiotic discovery void. MDPI 2020-11-30 /pmc/articles/PMC7760116/ /pubmed/33265975 http://dx.doi.org/10.3390/microorganisms8121897 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Perspective
Shitut, Shraddha
Bergman, Güniz Özer
Kros, Alexander
Rozen, Daniel E.
Claessen, Dennis
Use of Permanent Wall-Deficient Cells as a System for the Discovery of New-to-Nature Metabolites
title Use of Permanent Wall-Deficient Cells as a System for the Discovery of New-to-Nature Metabolites
title_full Use of Permanent Wall-Deficient Cells as a System for the Discovery of New-to-Nature Metabolites
title_fullStr Use of Permanent Wall-Deficient Cells as a System for the Discovery of New-to-Nature Metabolites
title_full_unstemmed Use of Permanent Wall-Deficient Cells as a System for the Discovery of New-to-Nature Metabolites
title_short Use of Permanent Wall-Deficient Cells as a System for the Discovery of New-to-Nature Metabolites
title_sort use of permanent wall-deficient cells as a system for the discovery of new-to-nature metabolites
topic Perspective
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760116/
https://www.ncbi.nlm.nih.gov/pubmed/33265975
http://dx.doi.org/10.3390/microorganisms8121897
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