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    Please use this identifier to cite or link to this item: http://ir.cnu.edu.tw/handle/310902800/31728

    標題: Discovery of McrA, a master regulator of Aspergillus secondary metabolism
    作者: Oakley, C. Elizabeth
    Ahuja, Manmeet
    Sun, Wei-Wen
    Entwistle, Ruth
    Akashi, Tomohiro
    Yaegashi, Junko
    Guo, Chun-Jun
    Cerqueira, Gustavo C.
    Wortman, Jennifer Russo
    Wang, Clay C. C.
    Chiang, Yi-Ming
    Oakley, Berl R.
    貢獻者: Univ Kansas, Dept Mol Biosci
    Univ Southern Calif, Sch Pharm
    Nagoya Univ, Div OMICS Anal
    Broad Inst MIT & Harvard, Genome Sequencing & Anal Program
    Univ Southern Calif, Dornsife Coll Letters Arts & Sci
    Chia Nan Univ Pharm & Sci, Dept Pharm
    Reliance Ind Ltd, Reliance Technol Grp
    Joint BioEnergy Inst
    Pacific Northwest Natl Lab
    Univ Calif San Francisco, Dept Bioengn & Therapeut Sci
    關鍵字: Biosynthetic Gene Clusters
    Nidulans Gpda Gene
    Filamentous Fungi
    Glyceraldehyde-3-Phosphate Dehydrogenase
    Heterologous Expression
    Aflatoxin Biosynthesis
    Chemical Diversity
    Structural Gene
    日期: 2017-01
    上傳時間: 2018-11-30 15:54:27 (UTC+8)
    出版者: Wiley-Blackwell
    摘要: 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 nidutans 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.
    關聯: Molecular Microbiology, v.103, n.2, pp.347-365
    Appears in Collections:[藥學系(所)] 期刊論文

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