Discovery of McrA, a Master Regulator of Aspergillus Secondary Metabolism

Overview

Journal Mol Microbiol

Specialties Microbiology
Molecular Biology

Date 2016 Oct 25

PMID 27775185

Citations 38

Authors

C Elizabeth Oakley

Manmeet Ahuja

Wei-Wen Sun

Ruth Entwistle

Tomohiro Akashi

Junko Yaegashi

Chun-Jun Guo

Gustavo C Cerqueira

Jennifer Russo Wortman

Clay C C Wang

Yi-Ming Chiang

Berl R Oakley

Affiliations

Soon will be listed here.

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 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.

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