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A novel locus for mycelial aggregation forms a gateway to improved Streptomyces cell factories

BACKGROUND: Streptomycetes produce a plethora of natural products including antibiotics and anticancer drugs, as well as many industrial enzymes. Their mycelial life style is a major bottleneck for industrial exploitation and over decades strain improvement programs have selected production strains...

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Detalles Bibliográficos
Autores principales: van Dissel, Dino, Claessen, Dennis, Roth, Martin, van Wezel, Gilles P
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4391728/
https://www.ncbi.nlm.nih.gov/pubmed/25889360
http://dx.doi.org/10.1186/s12934-015-0224-6
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author van Dissel, Dino
Claessen, Dennis
Roth, Martin
van Wezel, Gilles P
author_facet van Dissel, Dino
Claessen, Dennis
Roth, Martin
van Wezel, Gilles P
author_sort van Dissel, Dino
collection PubMed
description BACKGROUND: Streptomycetes produce a plethora of natural products including antibiotics and anticancer drugs, as well as many industrial enzymes. Their mycelial life style is a major bottleneck for industrial exploitation and over decades strain improvement programs have selected production strains with better growth properties. Uncovering the nature of the underlying mutations should allow the ready transfer of desirable traits to other production hosts. RESULTS: Here we report that the mat gene cluster, which was identified through reverse engineering of a non-pelleting mutant selected in a chemostat, is key to pellet formation of Streptomyces lividans. Deletion of matA or matB, which encode putative polysaccharide synthases, effects mycelial metamorphosis, with very small and open mycelia. Growth rate and productivity of the matAB null mutant were increased by over 60% as compared to the wild-type strain. CONCLUSION: Here, we present a way to counteract pellet formation by streptomycetes, which is one of the major bottlenecks in their industrial application. The mat locus is an ideal target for rational strain design approaches aimed at improving streptomycetes as industrial production hosts. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12934-015-0224-6) contains supplementary material, which is available to authorized users.
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spelling pubmed-43917282015-04-10 A novel locus for mycelial aggregation forms a gateway to improved Streptomyces cell factories van Dissel, Dino Claessen, Dennis Roth, Martin van Wezel, Gilles P Microb Cell Fact Research BACKGROUND: Streptomycetes produce a plethora of natural products including antibiotics and anticancer drugs, as well as many industrial enzymes. Their mycelial life style is a major bottleneck for industrial exploitation and over decades strain improvement programs have selected production strains with better growth properties. Uncovering the nature of the underlying mutations should allow the ready transfer of desirable traits to other production hosts. RESULTS: Here we report that the mat gene cluster, which was identified through reverse engineering of a non-pelleting mutant selected in a chemostat, is key to pellet formation of Streptomyces lividans. Deletion of matA or matB, which encode putative polysaccharide synthases, effects mycelial metamorphosis, with very small and open mycelia. Growth rate and productivity of the matAB null mutant were increased by over 60% as compared to the wild-type strain. CONCLUSION: Here, we present a way to counteract pellet formation by streptomycetes, which is one of the major bottlenecks in their industrial application. The mat locus is an ideal target for rational strain design approaches aimed at improving streptomycetes as industrial production hosts. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12934-015-0224-6) contains supplementary material, which is available to authorized users. BioMed Central 2015-04-01 /pmc/articles/PMC4391728/ /pubmed/25889360 http://dx.doi.org/10.1186/s12934-015-0224-6 Text en © van Dissel et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
van Dissel, Dino
Claessen, Dennis
Roth, Martin
van Wezel, Gilles P
A novel locus for mycelial aggregation forms a gateway to improved Streptomyces cell factories
title A novel locus for mycelial aggregation forms a gateway to improved Streptomyces cell factories
title_full A novel locus for mycelial aggregation forms a gateway to improved Streptomyces cell factories
title_fullStr A novel locus for mycelial aggregation forms a gateway to improved Streptomyces cell factories
title_full_unstemmed A novel locus for mycelial aggregation forms a gateway to improved Streptomyces cell factories
title_short A novel locus for mycelial aggregation forms a gateway to improved Streptomyces cell factories
title_sort novel locus for mycelial aggregation forms a gateway to improved streptomyces cell factories
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4391728/
https://www.ncbi.nlm.nih.gov/pubmed/25889360
http://dx.doi.org/10.1186/s12934-015-0224-6
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