Genomic Wake-Up Call: Activating Silent Biosynthetic Pathways for Novel Metabolites in Penicillium chrysogenum

Marta Samol

Research output: ThesisThesis fully internal (DIV)

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Abstract

Genomic Wake-Up Call:
Activating Silent Biosynthetic Pathways for Novel Metabolites in Penicillium chrysogenum

The filamentous fungus Penicillium chrysogenum, discovered by Alexander Fleming in 1928, is wildly used in industry for the production of β-lactams antibiotics. Antibiotics and other natural products (secondary metabolites) have many potential applications ranging from drugs to toxins with important medical and economical values. Recently, genome sequencing of P. chrysogenum uncovered many enzyme complexes that are capable of synthesizing such bioactive products: The genome specifies 20 Polyketides synthase (PKSs) and 11 Nonribosomal Peptide Synthetases (NRPSs), including two Polyketide Synthase-Nonribosomal Peptide Synthetase hybrids (HPNs). However, the majority of these genes remain not expressed under standard cultivation conditions. This research sought to exploit this source of potential novel secondary metabolites by awaking these silent biosynthetic pathways. This was achieved by interfering with global and epigenetic regulation and the chromatin landscape change. In addition, growth of P. chrysogenum under iron limited conditions induced the expression of three silent nrps that were identified as siderophore synthetases (Pss). This resulted in production of iron scavengers known as siderophores (Greek: "iron carrier"), including the all known classes (coprogens, fusarinines, and ferrichromes) and novel siderophores. Starting from genome mining, and by applying tools of epigenetic, genomic engineering or nutrition’s limitations strategies, in total 38 compounds including 11 novel metabolites were obtained from 16 silent biosynthetic pathways. Each of these metabolites might carry a unique bioactivity.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • University of Groningen
Supervisors/Advisors
  • Driessen, Arnold, Supervisor
Award date17-Apr-2015
Place of Publication[Groningen]
Publisher
Print ISBNs978-90-367-7724-7
Electronic ISBNs978-90-367-7723-0
Publication statusPublished - 2015

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