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Open AccessPerspective

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

1
Origins Centre, Nijenborgh 7, 9747 AG Groningen, The Netherlands
2
Institute of Biology, Leiden University, 2333 BE Leiden, The Netherlands
3
Leiden Institute of Chemistry, Leiden University, 2333 CC Leiden, The Netherlands
*
Authors to whom correspondence should be addressed.
Microorganisms 2020, 8(12), 1897; https://doi.org/10.3390/microorganisms8121897
Received: 6 November 2020 / Revised: 27 November 2020 / Accepted: 28 November 2020 / Published: 30 November 2020
(This article belongs to the Special Issue Microbial Secondary Metabolites and Biotechnology)
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. View Full-Text
Keywords: secondary metabolites; actinomycetes; protoplast fusion; novel compound discovery; cell wall-deficiency; heteroploidy secondary metabolites; actinomycetes; protoplast fusion; novel compound discovery; cell wall-deficiency; heteroploidy
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MDPI and ACS Style

Shitut, S.; Bergman, G.Ö.; Kros, A.; Rozen, D.E.; Claessen, D. Use of Permanent Wall-Deficient Cells as a System for the Discovery of New-to-Nature Metabolites. Microorganisms 2020, 8, 1897. https://doi.org/10.3390/microorganisms8121897

AMA Style

Shitut S, Bergman GÖ, Kros A, Rozen DE, Claessen D. Use of Permanent Wall-Deficient Cells as a System for the Discovery of New-to-Nature Metabolites. Microorganisms. 2020; 8(12):1897. https://doi.org/10.3390/microorganisms8121897

Chicago/Turabian Style

Shitut, Shraddha; Bergman, Güniz Ö.; Kros, Alexander; Rozen, Daniel E.; Claessen, Dennis. 2020. "Use of Permanent Wall-Deficient Cells as a System for the Discovery of New-to-Nature Metabolites" Microorganisms 8, no. 12: 1897. https://doi.org/10.3390/microorganisms8121897

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