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Engineering of the Filamentous Fungus Penicillium chrysogenum as Cell Factory for Natural Products

Guzman-Chavez, F., Zwahlen, R. D., Bovenberg, R. A. L. & Driessen, A. J. M., 15-Nov-2018, In : Frontiers in Microbiology. 9, 25 p., 2768.

Research output: Contribution to journalReview articleAcademicpeer-review

Penicillium chrysogenum (renamed P. rubens) is the most studied member of a family of more than 350 Penicillium species that constitute the genus. Since the discovery of penicillin by Alexander Fleming, this filamentous fungus is used as a commercial beta-lactam antibiotic producer. For several decades, P. chrysogenum was subjected to a classical strain improvement (CSI) program to increase penicillin titers. This resulted in a massive increase in the penicillin production capacity, paralleled by the silencing of several other biosynthetic gene clusters (BGCs), causing a reduction in the production of a broad range of BGC encoded natural products (NPs). Several approaches have been used to restore the ability of the penicillin production strains to synthetize the NPs lost during the CSI. Here, we summarize various re-activation mechanisms of BGCs, and how interference with regulation can be used as a strategy to activate or silence BGCs in filamentous fungi. To further emphasize the versatility of P. chrysogenum as a fungal production platform for NPs with potential commercial value, protein engineering of biosynthetic enzymes is discussed as a tool to develop de novo BGC pathways for new NPs.

Original languageEnglish
Article number2768
Number of pages25
JournalFrontiers in Microbiology
Volume9
Publication statusPublished - 15-Nov-2018

    Keywords

  • Penicillium chrysogenum, natural products, nonribosomal peptides, polyketides, gene activation, biosynthetic gene clusters, cell factory, NONRIBOSOMAL PEPTIDE SYNTHETASE, BIOSYNTHETIC GENE CLUSTERS, ACYL CARRIER PROTEIN, SECONDARY METABOLITE BIOSYNTHESIS, ISOPENICILLIN-N ACYLTRANSFERASE, MODULAR POLYKETIDE SYNTHASES, MBTH-LIKE PROTEINS, ASPERGILLUS-NIDULANS, TRANSCRIPTION FACTOR, CHEMICAL DIVERSITY

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