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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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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. |
format | Online Article Text |
id | pubmed-7760116 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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