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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2009-2-2
pubmed:abstractText
The biosynthesis of the beta-lactam antibiotic penicillin is an excellent model for the study of secondary metabolites produced by filamentous fungi due to the good background knowledge on the biochemistry and molecular genetics of the beta-lactam producing microorganisms. The three genes (pcbAB, pcbC, penDE) encoding enzymes of the penicillin pathway in Penicillium chrysogenum are clustered, but no penicillin pathway-specific regulators have been found in the genome region that contains the penicillin gene cluster. The biosynthesis of this beta-lactam is controlled by global regulators of secondary metabolism rather than by a pathway-specific regulator. In this work we have identified the gene encoding the secondary metabolism global regulator LaeA in P. chrysogenum (PcLaeA), a nuclear protein with a methyltransferase domain. The PclaeA gene is present as a single copy in the genome of low and high-penicillin producing strains and is not located in the 56.8-kb amplified region occurring in high-penicillin producing strains. Overexpression of the PclaeA gene gave rise to a 25% increase in penicillin production. PclaeA knock-down mutants exhibited drastically reduced levels of penicillin gene expression and antibiotic production and showed pigmentation and sporulation defects, but the levels of roquefortine C produced and the expression of the dmaW involved in roquefortine biosynthesis remained similar to those observed in the wild-type parental strain. The lack of effect on the synthesis of roquefortine is probably related to the chromatin arrangement in the low expression roquefortine promoters as compared to the bidirectional pbcAB-pcbC promoter region involved in penicillin biosynthesis. These results evidence that PcLaeA not only controls some secondary metabolism gene clusters, but also asexual differentiation in P. chrysogenum.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1638-6183
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
91
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
214-25
pubmed:meshHeading
pubmed-meshheading:18952140-Amino Acid Sequence, pubmed-meshheading:18952140-Cluster Analysis, pubmed-meshheading:18952140-Computational Biology, pubmed-meshheading:18952140-Gene Dosage, pubmed-meshheading:18952140-Gene Expression Regulation, pubmed-meshheading:18952140-Genes, Fungal, pubmed-meshheading:18952140-Genes, Regulator, pubmed-meshheading:18952140-Heterocyclic Compounds with 4 or More Rings, pubmed-meshheading:18952140-Indoles, pubmed-meshheading:18952140-Molecular Sequence Data, pubmed-meshheading:18952140-Multigene Family, pubmed-meshheading:18952140-Mutation, pubmed-meshheading:18952140-Nuclear Proteins, pubmed-meshheading:18952140-Penicillins, pubmed-meshheading:18952140-Penicillium chrysogenum, pubmed-meshheading:18952140-Pigmentation, pubmed-meshheading:18952140-Piperazines, pubmed-meshheading:18952140-Plasmids, pubmed-meshheading:18952140-Protein Structure, Tertiary, pubmed-meshheading:18952140-Sequence Homology, Amino Acid, pubmed-meshheading:18952140-Spores, Fungal, pubmed-meshheading:18952140-Transcription, Genetic
pubmed:year
2009
pubmed:articleTitle
The global regulator LaeA controls penicillin biosynthesis, pigmentation and sporulation, but not roquefortine C synthesis in Penicillium chrysogenum.
pubmed:affiliation
Instituto de Biotecnología, León, Spain.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't