Discovery of McrA, a master regulator of Aspergillus secondary metabolism

doi:10.1111/mmi.13562

CNU IR > Pharmacy and Science > Dept. of Pharmacy > Periodical Articles > Item 310902800/31728

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Title:	Discovery of McrA, a master regulator of Aspergillus secondary metabolism
Authors:	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.
Contributors:	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
Keywords:	Biosynthetic Gene Clusters Nidulans Gpda Gene Filamentous Fungi Glyceraldehyde-3-Phosphate Dehydrogenase Heterologous Expression Aflatoxin Biosynthesis Chemical Diversity Natural-Products Structural Gene System
Date:	2017-01
Issue Date:	2018-11-30 15:54:27 (UTC+8)
Publisher:	Wiley-Blackwell
Abstract:	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.
Relation:	Molecular Microbiology, v.103, n.2, pp.347-365
Appears in Collections:	[Dept. of Pharmacy] Periodical Articles

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