Journal Article

Genome sequencing and analysis of the filamentous fungus Penicillium chrysogenum

Nierman, William C, Albang, Richard, Nijland, Jeroen G, Heijne, Wilbert H M, Bovenberg, Roel A L, Albermann, Kaj, Martín, Juan F, Badger, Jonathan H, Pronk, Jack T, W Kiel, Jan A K, Wagner, Christian, Veenhuis, Marten, Joardar, Vinita, Fedorova, Natalie D, Garcia-Estrada, Carlos, Harris, Diana M, Wortman, Jennifer, von Döhren, Hans, M Driessen, Arnold J, van Peij, Noël N M E, Roubos, Johannes A, van der Klei, Ida J, Kovalchuk, Andriy, Daran, Jean-Marc, van den Berg, Marco A

2008

Overview

Penicillins and derived β-lactam antibiotics are essential in healthcare. To gain more insight into penicillin synthesis van den Berg and colleagues sequence and analyze the genome and transcriptome of the filamentous fungus Penicillium chrysogenum . 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 α-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 β-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.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: Agriculture / Base Sequence / Bioinformatics / Biological and medical sciences / Biology of microorganisms of confirmed or potential industrial interest / Biomedical and Life Sciences / Biomedical Engineering/Biotechnology / Biomedicine / Biosynthesis / Biotechnology / Chromosome Mapping - methods / Deoxyribonucleic acid / DNA / DNA microarrays / DNA sequencing / Fundamental and applied biological sciences. Psychology / Fungal Proteins - genetics / Fungi / Genetic aspects / Genetics / Genome, Fungal - genetics / Genomics / Life Sciences / Methods / Mission oriented research / Molecular Sequence Data / Nucleotide sequencing / Penicillin / Penicillin G - metabolism / Penicillium chrysogenum / Penicillium chrysogenum - genetics / Process engineering / Sequence Analysis, DNA - methods / Transcription Factors - genetics / Transport processes