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Arnold J.M. Driessen  - - - 
Top co-authors See all
Herman S. Overkleeft

435 shared publications

Universiteit Leiden

B L Feringa

363 shared publications

Centre for Systems Chemistry; Stratingh Institute for Chemistry; University of Groningen; Nijenborgh 4 9747 AG Groningen The Netherlands

Dörte Becher

268 shared publications

Institute of Microbiology, Center for Functional Genomics of Microbes, University of Greifswald, Greifswald, Germany

Bert Poolman

230 shared publications

Department of Biochemistry, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, The Netherlands

Michael Hecker

207 shared publications

Institute of Microbiology; Ernst-Moritz-Arndt-University Greifswald; 17489 Greifswald Germany

Publication Record
Distribution of Articles published per year 
(1994 - 2018)
Total number of journals
published in
Publications See all
Article 0 Reads 0 Citations Synthetic Minimal Cell: Self-Reproduction of the Boundary Layer Marten Exterkate, Arnold J. M. Driessen Published: 13 March 2019
ACS Omega, doi: 10.1021/acsomega.8b02955
DOI See at publisher website
Article 0 Reads 0 Citations Identification of the decumbenone biosynthetic gene cluster in Penicillium decumbens and the importance for production o... Sietske Grijseels, Carsten Pohl, Zahida Wasil, Yvonne Nygård... Published: 19 December 2018
Fungal Biology and Biotechnology, doi: 10.1186/s40694-018-0063-4
DOI See at publisher website PubMed View at PubMed ABS Show/hide abstract
Filamentous fungi are important producers of secondary metabolites, low molecular weight molecules that often have bioactive properties. Calbistrin A is a secondary metabolite with an interesting structure that was recently found to have bioactivity against leukemia cells. It consists of two polyketides linked by an ester bond: a bicyclic decalin containing polyketide with structural similarities to lovastatin, and a linear 12 carbon dioic acid structure. Calbistrin A is known to be produced by several uniseriate black Aspergilli, Aspergillus versicolor-related species, and Penicillia. Penicillium decumbens produces calbistrin A and B as well as several putative intermediates of the calbistrin pathway, such as decumbenone A-B and versiol. A comparative genomics study focused on the polyketide synthase (PKS) sets found in three full genome sequence calbistrin producing fungal species, P. decumbens, A. aculeatus and A. versicolor, resulted in the identification of a novel, putative 13-membered calbistrin producing gene cluster (calA to calM). Implementation of the CRISPR/Cas9 technology in P. decumbens allowed the targeted deletion of genes encoding a polyketide synthase (calA), a major facilitator pump (calB) and a binuclear zinc cluster transcription factor (calC). Detailed metabolic profiling, using UHPLC-MS, of the ∆calA (PKS) and ∆calC (TF) strains confirmed the suspected involvement in calbistrin productions as neither strains produced calbistrin nor any of the putative intermediates in the pathway. Similarly analysis of the excreted metabolites in the ∆calB (MFC-pump) strain showed that the encoded pump was required for efficient export of calbistrin A and B. Here we report the discovery of a gene cluster (calA-M) involved in the biosynthesis of the polyketide calbistrin in P. decumbens. Targeted gene deletions proved the involvement of CalA (polyketide synthase) in the biosynthesis of calbistrin, CalB (major facilitator pump) for the export of calbistrin A and B and CalC for the transcriptional regulation of the cal-cluster. This study lays the foundation for further characterization of the calbistrin biosynthetic pathway in multiple species and the development of an efficient calbistrin producing cell factory.
Article 0 Reads 0 Citations Engineering of the Filamentous Fungus Penicillium chrysogenum as Cell Factory for Natural Products Fernando Guzmán-Chávez, Reto D. Zwahlen, Roel A. L. Bovenber... Published: 15 November 2018
Frontiers in Microbiology, doi: 10.3389/fmicb.2018.02768
DOI See at publisher website PubMed View at PubMed ABS Show/hide abstract
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 β-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.
Article 0 Reads 1 Citation Laboratory evolution of a glucose-phosphorylation-deficient, arabinose-fermenting S. cerevisiae strain reveals mutations... Maarten D Verhoeven, Jasmine M Bracher, Jeroen G Nijland, Jo... Published: 01 September 2018
FEMS Yeast Research, doi: 10.1093/femsyr/foy062
DOI See at publisher website PubMed View at PubMed ABS Show/hide abstract
Cas9-assisted genome editing was used to construct an engineered glucose-phosphorylation-negative S. cerevisiae strain, expressing the Lactobacillus plantaruml-arabinose pathway and the Penicillium chrysogenum transporter PcAraT. This strain, which showed a growth rate of 0.26 h-1 on l-arabinose in aerobic batch cultures, was subsequently evolved for anaerobic growth on l-arabinose in the presence of d-glucose and d-xylose. In four strains isolated from two independent evolution experiments the galactose-transporter gene GAL2 had been duplicated, with all alleles encoding Gal2N376T or Gal2N376I substitutions. In one strain, a single GAL2 allele additionally encoded a Gal2T89I substitution, which was subsequently also detected in the independently evolved strain IMS0010. In 14C-sugar-transport assays, Gal2N376S, Gal2N376T and Gal2N376I substitutions showed a much lower glucose sensitivity of l-arabinose transport and a much higher Km for d-glucose transport than wild-type Gal2. Introduction of the Gal2N376I substitution in a non-evolved strain enabled growth on l-arabinose in the presence of d-glucose. Gal2N376T, T89I and Gal2T89I variants showed a lower Km for l-arabinose and a higher Km for d-glucose than wild-type Gal2, while reverting Gal2N376T, T89I to Gal2N376 in an evolved strain negatively affected anaerobic growth on l-arabinose. This study indicates that optimal conversion of mixed-sugar feedstocks may require complex 'transporter landscapes', consisting of sugar transporters with complementary kinetic and regulatory properties.
BOOK-CHAPTER 0 Reads 3 Citations Genome Editing in Penicillium chrysogenum Using Cas9 Ribonucleoprotein Particles Carsten Pohl, László Mózsik, Arnold J. M. Driessen, Roel A. ... Published: 13 May 2018
Alcohol, doi: 10.1007/978-1-4939-7795-6_12
DOI See at publisher website
Article 0 Reads 1 Citation Deregulation of secondary metabolism in a histone deacetylase mutant of Penicillium chrysogenum Fernando Guzmán-Chávez, Oleksandr Salo, Marta Samol, Marco R... Published: 24 March 2018
MicrobiologyOpen, doi: 10.1002/mbo3.598
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The Pc21 g14570 gene of Penicillium chrysogenum encodes an ortholog of a class 2 histone deacetylase termed HdaA which may play a role in epigenetic regulation of secondary metabolism. Deletion of the hdaA gene induces a significant pleiotropic effect on the expression of a set of polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS)‐encoding genes. The deletion mutant exhibits a decreased conidial pigmentation that is related to a reduced expression of the PKS gene Pc21 g16000 (pks17) responsible for the production of the pigment precursor naphtha‐γ‐pyrone. Moreover, the hdaA deletion caused decreased levels of the yellow pigment chrysogine that is associated with the downregulation of the NRPS‐encoding gene Pc21 g12630 and associated biosynthetic gene cluster. In contrast, transcriptional activation of the sorbicillinoids biosynthetic gene cluster occurred concomitantly with the overproduction of associated compounds . A new compound was detected in the deletion strain that was observed only under conditions of sorbicillinoids production, suggesting crosstalk between biosynthetic gene clusters. Our present results show that an epigenomic approach can be successfully applied for the activation of secondary metabolism in industrial strains of P. chrysogenum.