Systems Biology of the Secondary Metabolism in Filamentous Fungi
Doctoral thesis, 2018
Jens Christian Froslev Nielsen
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
Penicillium arizonense, a new, genome sequenced fungal species, reveals a high chemical diversity in secreted metabolites
Scientific Reports,; Vol. 6(2016)
Global analysis of biosynthetic gene clusters reveals vast potential of secondary metabolite production in Penicillium species
Nature Microbiology,; Vol. 2(2017)
Physiological characterization of secondary metabolite producing Penicillium cell factories
Fungal Biology and Biotechnology,; Vol. 4(2017)p. 8-
Development of fungal cell factories for the production of secondary metabolites: Linking genomics and metabolism
Synthetic and Systems Biotechnology,; Vol. 2(2017)p. 5-12
Nielsen, J. C., Prigent, S., Grijseels, S., Workman, M., Ji, B., Nielsen, J. (2018). Metabolic regulation of filamentous fungi is tailored for production of secondary metabolites.
Prigent, S., Nielsen, J. C., Frisvad, J. C., and Nielsen, J. (2018). Automatic reconstruction of 24 Penicillium genome-scale metabolic models shows diversity in the secondary metabolism.
This PhD thesis represents an endeavour to increase the understanding of the natural production of antibiotics in filamentous fungi. We provide novel insight on how to speed up the drug discovery process, from screening of microbial biodiversity to industrial exploitation. The genomes of uncharacterized filamentous fungi were sequenced, and a computational analysis pipeline was developed to identify and annotate the genes responsible for the synthesis of antibiotics. Our investigations demonstrated that fungal biodiversity possesses a previously untapped potential for production of antibiotics, and based on our predictions, we experimentally identified a novel compound from the antifungal class of antibiotics called yanuthones.
Further investigations of fungal metabolism were based on the quantification of gene expression, and allowed us to identify important pathways that provide building blocks for the biosynthesis of antibiotics. Modifying the genes controlling these pathways constitute a promising strategy for improving the natural production capabilities of fungi to enable industrial production of new antibiotics.
This thesis suggests that previously unknown antibiotics can be discovered from understudied fungi, and that genetic modifications of key metabolic pathways identified in this work, could enable development of industrial antibiotics production processes.
Bioinformatics and Systems Biology
C3SE (Chalmers Centre for Computational Science and Engineering)
Innovation and entrepreneurship
Areas of Advance
Life Science Engineering (2010-2018)
Doktorsavhandlingar vid Chalmers tekniska högskola. Ny serie: 4352
Sal KA, Kemihuset (Chalmers, Johanneberg campus)
Opponent: Mikael Rørdam Andersen, Technical University of Denmark