Article abstract
Nature Biotechnology 26, 1161 - 1168 (2008)
Published online: 28 September 2008 | doi:10.1038/nbt.1498
Genome sequencing and analysis of the filamentous fungus Penicillium chrysogenum
Marco A van den Berg1, Richard Albang2, Kaj Albermann2, Jonathan H Badger3, Jean-Marc Daran4,5, Arnold J M Driessen4,6, Carlos Garcia-Estrada7, Natalie D Fedorova3, Diana M Harris4,5, Wilbert H M Heijne8, Vinita Joardar3, Jan A K W Kiel9, Andriy Kovalchuk6, Juan F Martín7,10, William C Nierman3,11, Jeroen G Nijland6, Jack T Pronk4,5, Johannes A Roubos8, Ida J van der Klei4,9, Noël N M E van Peij8, Marten Veenhuis9, Hans von Döhren12, Christian Wagner2, Jennifer Wortman3 & Roel A L Bovenberg1
Abstract
Industrial penicillin production with the filamentous fungus Penicillium chrysogenum is based on an unprecedented effort in microbial strain improvement. To gain more insight into penicillin synthesis, we sequenced the 32.19 Mb genome of P. chrysogenum Wisconsin54-1255 and identified numerous genes responsible for key steps in penicillin production. DNA microarrays were used to compare the transcriptomes of the sequenced strain and a penicillinG high-producing strain, grown in the presence and absence of the side-chain precursor phenylacetic acid. Transcription of genes involved in biosynthesis of valine, cysteine and 
-aminoadipic acid—precursors for penicillin biosynthesis—as well as of genes encoding microbody proteins, was increased in the high-producing strain. Some gene products were shown to be directly controlling 
-lactam output. Many key cellular transport processes involving penicillins and intermediates remain to be characterized at the molecular level. Genes predicted to encode transporters were strongly overrepresented among the genes transcriptionally upregulated under conditions that stimulate penicillinG production, illustrating potential for future genomics-driven metabolic engineering.
- DSM Anti Infectives, PO Box 425, 2600 AK Delft, The Netherlands.
- Biomax Informatics AG, Lochhamer Str. 9, D- 82152 Martinsried, Germany.
- The J. Craig Venter Institute for Genomic Research, 9712 Medical Center Drive, Rockville, Maryland 20850, USA.
- Kluyver Centre for Genomics of Industrial Fermentation, Julianalaan 67, 2628 BC Delft, The Netherlands.
- Department of Biotechnology, Delft University of Technology, Julianalaan 67, 2628 BC Delft, The Netherlands.
- Molecular Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Kerklaan 30, 9751 NN Haren, The Netherlands.
- INBIOTEC, Instituto de Biotecnología de León, Avda. Real no. 1, Parque Científico de León, 24006 León, Spain.
- DSM Food Specialties, PO Box 1, 2600 MA Delft, The Netherlands.
- Molecular Cell Biology, Groningen Biomolecular Sciences and Biotechnology Institute, Kerklaan 30, 9751 NN Haren, The Netherlands.
- Area de Microbiologia, Departamento de Biologia Molecular, Facultad de CC. Biologicas y Ambientales, Universidad de Leon, Campus de Vegazana s/n 24071, Leon, Spain.
- The George Washington University School of Medicine, Department of Biochemistry and Molecular Biology, 2300 Eye Street NW, Washington, DC 20037, USA.
- Institut für Chemie, Universität Berlin, Sekretariat OE2, Franklinstrasse 29, 10623 Berlin, Germany.
Correspondence to: Marco A van den Berg1 e-mail: Marco.Berg-van-den@DSM.com
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