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|標題: ||Discovery of McrA, a master regulator of Aspergillus secondary metabolism|
|作者: ||Oakley, C. Elizabeth|
Cerqueira, Gustavo C.
Wortman, Jennifer Russo
Wang, Clay C. C.
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
|上傳時間: ||2018-11-30 15:54:27 (UTC+8)|
|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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