Discovery of McrA, a master regulator ofAspergillussecondary metabolism
Autor: | Wei-Wen Sun, Gustavo C. Cerqueira, Jennifer R. Wortman, Berl R. Oakley, Tomohiro Akashi, C. Elizabeth Oakley, Chun-Jun Guo, Yi-Ming Chiang, Manmeet Ahuja, Clay C. C. Wang, Junko Yaegashi, Ruth Entwistle |
---|---|
Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Regulation of gene expression Genetics biology 030106 microbiology Structural gene biology.organism_classification Microbiology 03 medical and health sciences 030104 developmental biology Aspergillus nidulans Transcription (biology) Secondary metabolism Molecular Biology Gene Transcription factor Genetic screen |
Zdroj: | Molecular Microbiology. 103:347-365 |
ISSN: | 0950-382X |
Popis: | Fungal secondary metabolites (SMs) are extremely important in medicine and agriculture, but regulation of their biosynthesis is incompletely understood. We have developed a genetic screen in Aspergillus nidulans for negative regulators of fungal SM gene clusters and we have used this screen to isolate mutations that upregulate transcription of the non-ribosomal peptide synthetase gene required for nidulanin A biosynthesis. Several of these mutations are allelic and we have identified the mutant gene by genome sequencing. The gene, which we designate mcrA, is conserved but uncharacterized, and it encodes a putative transcription factor. Metabolite profiles of mcrA deletant, mcrA overexpressing, and parental strains reveal that mcrA regulates at least ten SM gene clusters. Deletion of mcrA stimulates SM production even in strains carrying a deletion of the SM regulator laeA, and deletion of mcrA homologs in Aspergillus terreus and Penicillum canescens alters the secondary metabolite profile of these organisms. Deleting mcrA in a genetic dereplication strain has allowed us to discover two novel compounds as well as an antibiotic not known to be produced by A. nidulans. Deletion of mcrA upregulates transcription of hundreds of genes including many that are involved in secondary metabolism, while downregulating a smaller number of genes. This article is protected by copyright. All rights reserved. |
Databáze: | OpenAIRE |
Externí odkaz: |