Physiological characterization of secondary metabolite producing Penicillium cell factories

Sietske Grijseels, Jens Nielsen, Jens Nielsen, Thomas Ostenfeld Larsen, Jens Christian Frisvad, Kristian Fog Nielsen, Rasmus John Normand Frandsen, Mhairi Workman

Research output: Contribution to journalJournal articleResearchpeer-review

736 Downloads (Orbit)

Abstract

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. 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. 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.
Original languageEnglish
JournalFungal Biology and Biotechnology
Volume4
Issue number8
Number of pages12
ISSN2054-3085
DOIs
Publication statusPublished - 2017

Bibliographical note

© The Author(s) 2017. This 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.

Keywords

  • Cell factory
  • Penicillium
  • Physiology
  • Secondary metabolite
  • Submerged fermentation

Fingerprint

Dive into the research topics of 'Physiological characterization of secondary metabolite producing Penicillium cell factories'. Together they form a unique fingerprint.

Cite this