A Penicillium rubens platform strain for secondary metabolite production

Carsten Pohl, Fabiola Polli, Tabea Schütze, Annarita Viggiano, László Mózsik, Sascha Jung, Maaike de Vries, Roel A L Bovenberg, Vera Meyer, Arnold J M Driessen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

5 Citations (Scopus)
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Abstract

We present a Penicillium rubens strain with an industrial background in which the four highly expressed biosynthetic gene clusters (BGC) required to produce penicillin, roquefortine, chrysogine and fungisporin were removed. This resulted in a minimal secondary metabolite background. Amino acid pools under steady-state growth conditions showed reduced levels of methionine and increased intracellular aromatic amino acids. Expression profiling of remaining BGC core genes and untargeted mass spectrometry did not identify products from uncharacterized BGCs. This platform strain was repurposed for expression of the recently identified polyketide calbistrin gene cluster and achieved high yields of decumbenone A, B and C. The penicillin BGC could be restored through in vivo assembly with eight DNA segments with short overlaps. Our study paves the way for fast combinatorial assembly and expression of biosynthetic pathways in a fungal strain with low endogenous secondary metabolite burden.

Original languageEnglish
Article number7630
Number of pages16
JournalScientific Reports
Volume10
Issue number1
DOIs
Publication statusPublished - 1-Dec-2020

Keywords

  • NADPH METABOLISM
  • GENE CLUSTERS
  • BIOSYNTHESIS
  • GENOME
  • EXPRESSION
  • GROWTH
  • OPTIMIZATION
  • METABOLOMICS
  • DISCOVERY
  • PATHWAY

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