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| 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
Natural-Products
Structural Gene
System |
| 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 |
| 顯示於類別: | [藥學系(所)] 期刊論文
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