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A chromatogram-simplified Streptomyces albus host for heterologous production of natural products

Cloning natural product biosynthetic gene clusters from cultured or uncultured sources and their subsequent expression by genetically tractable heterologous hosts is an essential strategy for the elucidation and characterisation of novel microbial natural products. The availability of suitable expre...

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Detalles Bibliográficos
Autores principales: Fazal, Asif, Thankachan, Divya, Harris, Ellie, Seipke, Ryan F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7089911/
https://www.ncbi.nlm.nih.gov/pubmed/31781915
http://dx.doi.org/10.1007/s10482-019-01360-x
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author Fazal, Asif
Thankachan, Divya
Harris, Ellie
Seipke, Ryan F.
author_facet Fazal, Asif
Thankachan, Divya
Harris, Ellie
Seipke, Ryan F.
author_sort Fazal, Asif
collection PubMed
description Cloning natural product biosynthetic gene clusters from cultured or uncultured sources and their subsequent expression by genetically tractable heterologous hosts is an essential strategy for the elucidation and characterisation of novel microbial natural products. The availability of suitable expression hosts is a critical aspect of this workflow. In this work, we mutagenised five endogenous biosynthetic gene clusters from Streptomyces albus S4, which reduced the complexity of chemical extracts generated from the strain and eliminated antifungal and antibacterial bioactivity. We showed that the resulting quintuple mutant can express foreign biosynthetic gene clusters by heterologously producing actinorhodin, cinnamycin and prunustatin. We envisage that our strain will be a useful addition to the growing suite of heterologous expression hosts available for exploring microbial secondary metabolism. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10482-019-01360-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-70899112020-03-26 A chromatogram-simplified Streptomyces albus host for heterologous production of natural products Fazal, Asif Thankachan, Divya Harris, Ellie Seipke, Ryan F. Antonie Van Leeuwenhoek Original Paper Cloning natural product biosynthetic gene clusters from cultured or uncultured sources and their subsequent expression by genetically tractable heterologous hosts is an essential strategy for the elucidation and characterisation of novel microbial natural products. The availability of suitable expression hosts is a critical aspect of this workflow. In this work, we mutagenised five endogenous biosynthetic gene clusters from Streptomyces albus S4, which reduced the complexity of chemical extracts generated from the strain and eliminated antifungal and antibacterial bioactivity. We showed that the resulting quintuple mutant can express foreign biosynthetic gene clusters by heterologously producing actinorhodin, cinnamycin and prunustatin. We envisage that our strain will be a useful addition to the growing suite of heterologous expression hosts available for exploring microbial secondary metabolism. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10482-019-01360-x) contains supplementary material, which is available to authorized users. Springer International Publishing 2019-11-28 2020 /pmc/articles/PMC7089911/ /pubmed/31781915 http://dx.doi.org/10.1007/s10482-019-01360-x Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Paper
Fazal, Asif
Thankachan, Divya
Harris, Ellie
Seipke, Ryan F.
A chromatogram-simplified Streptomyces albus host for heterologous production of natural products
title A chromatogram-simplified Streptomyces albus host for heterologous production of natural products
title_full A chromatogram-simplified Streptomyces albus host for heterologous production of natural products
title_fullStr A chromatogram-simplified Streptomyces albus host for heterologous production of natural products
title_full_unstemmed A chromatogram-simplified Streptomyces albus host for heterologous production of natural products
title_short A chromatogram-simplified Streptomyces albus host for heterologous production of natural products
title_sort chromatogram-simplified streptomyces albus host for heterologous production of natural products
topic Original Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7089911/
https://www.ncbi.nlm.nih.gov/pubmed/31781915
http://dx.doi.org/10.1007/s10482-019-01360-x
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