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Physiological characterization of secondary metabolite producing Penicillium cell factories

BACKGROUND: Penicillium species are important producers of bioactive secondary metabolites. However, the immense diversity of the fungal kingdom is only scarcely represented in industrial bioprocesses and the upscaling of compound production remains a costly and labor intensive challenge. In order t...

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Autores principales: Grijseels, Sietske, Nielsen, Jens Christian, Nielsen, Jens, Larsen, Thomas Ostenfeld, Frisvad, Jens Christian, Nielsen, Kristian Fog, Frandsen, Rasmus John Normand, Workman, Mhairi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5644182/
https://www.ncbi.nlm.nih.gov/pubmed/29075506
http://dx.doi.org/10.1186/s40694-017-0036-z
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author Grijseels, Sietske
Nielsen, Jens Christian
Nielsen, Jens
Larsen, Thomas Ostenfeld
Frisvad, Jens Christian
Nielsen, Kristian Fog
Frandsen, Rasmus John Normand
Workman, Mhairi
author_facet Grijseels, Sietske
Nielsen, Jens Christian
Nielsen, Jens
Larsen, Thomas Ostenfeld
Frisvad, Jens Christian
Nielsen, Kristian Fog
Frandsen, Rasmus John Normand
Workman, Mhairi
author_sort Grijseels, Sietske
collection PubMed
description BACKGROUND: Penicillium species are important producers of bioactive secondary metabolites. However, the immense diversity of the fungal kingdom is only scarcely represented in industrial bioprocesses and the upscaling of compound production remains a costly and labor intensive challenge. In order to facilitate the development of novel secondary metabolite producing processes, two routes are typically explored: optimization of the native producer or transferring the enzymatic pathway into a heterologous host. Recent genome sequencing of ten Penicillium species showed the vast amount of secondary metabolite gene clusters present in their genomes, and makes them accessible for rational strain improvement. In this study, we aimed to characterize the potential of these ten Penicillium species as native producing cell factories by testing their growth performance and secondary metabolite production in submerged cultivations. RESULTS: Cultivation of the fungal species in controlled submerged bioreactors showed that the ten wild type Penicillium species had promising, highly reproducible growth characteristics in two different media. Analysis of the secondary metabolite production using liquid chromatography coupled with high resolution mass spectrometry proved that the species produced a broad range of secondary metabolites, at different stages of the fermentations. Metabolite profiling for identification of the known compounds resulted in identification of 34 metabolites; which included several with bioactive properties such as antibacterial, antifungal and anti-cancer activities. Additionally, several novel species–metabolite relationships were found. CONCLUSIONS: This study demonstrates that the fermentation characteristics and the highly reproducible performance in bioreactors of ten recently genome sequenced Penicillium species should be considered as very encouraging for the application of native hosts for production via submerged fermentation. The results are particularly promising for the potential development of the ten analysed Penicillium species for production of novel bioactive compounds via submerged fermentations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40694-017-0036-z) contains supplementary material, which is available to authorized users.
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spelling pubmed-56441822017-10-26 Physiological characterization of secondary metabolite producing Penicillium cell factories Grijseels, Sietske Nielsen, Jens Christian Nielsen, Jens Larsen, Thomas Ostenfeld Frisvad, Jens Christian Nielsen, Kristian Fog Frandsen, Rasmus John Normand Workman, Mhairi Fungal Biol Biotechnol Research BACKGROUND: Penicillium species are important producers of bioactive secondary metabolites. However, the immense diversity of the fungal kingdom is only scarcely represented in industrial bioprocesses and the upscaling of compound production remains a costly and labor intensive challenge. In order to facilitate the development of novel secondary metabolite producing processes, two routes are typically explored: optimization of the native producer or transferring the enzymatic pathway into a heterologous host. Recent genome sequencing of ten Penicillium species showed the vast amount of secondary metabolite gene clusters present in their genomes, and makes them accessible for rational strain improvement. In this study, we aimed to characterize the potential of these ten Penicillium species as native producing cell factories by testing their growth performance and secondary metabolite production in submerged cultivations. RESULTS: Cultivation of the fungal species in controlled submerged bioreactors showed that the ten wild type Penicillium species had promising, highly reproducible growth characteristics in two different media. Analysis of the secondary metabolite production using liquid chromatography coupled with high resolution mass spectrometry proved that the species produced a broad range of secondary metabolites, at different stages of the fermentations. Metabolite profiling for identification of the known compounds resulted in identification of 34 metabolites; which included several with bioactive properties such as antibacterial, antifungal and anti-cancer activities. Additionally, several novel species–metabolite relationships were found. CONCLUSIONS: This study demonstrates that the fermentation characteristics and the highly reproducible performance in bioreactors of ten recently genome sequenced Penicillium species should be considered as very encouraging for the application of native hosts for production via submerged fermentation. The results are particularly promising for the potential development of the ten analysed Penicillium species for production of novel bioactive compounds via submerged fermentations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40694-017-0036-z) contains supplementary material, which is available to authorized users. BioMed Central 2017-10-17 /pmc/articles/PMC5644182/ /pubmed/29075506 http://dx.doi.org/10.1186/s40694-017-0036-z Text en © The Author(s) 2017 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. 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
Grijseels, Sietske
Nielsen, Jens Christian
Nielsen, Jens
Larsen, Thomas Ostenfeld
Frisvad, Jens Christian
Nielsen, Kristian Fog
Frandsen, Rasmus John Normand
Workman, Mhairi
Physiological characterization of secondary metabolite producing Penicillium cell factories
title Physiological characterization of secondary metabolite producing Penicillium cell factories
title_full Physiological characterization of secondary metabolite producing Penicillium cell factories
title_fullStr Physiological characterization of secondary metabolite producing Penicillium cell factories
title_full_unstemmed Physiological characterization of secondary metabolite producing Penicillium cell factories
title_short Physiological characterization of secondary metabolite producing Penicillium cell factories
title_sort physiological characterization of secondary metabolite producing penicillium cell factories
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5644182/
https://www.ncbi.nlm.nih.gov/pubmed/29075506
http://dx.doi.org/10.1186/s40694-017-0036-z
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