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Overexpression of an LaeA-like Methyltransferase Upregulates Secondary Metabolite Production in Aspergillus nidulans.


ABSTRACT: Fungal secondary metabolites (SMs) include medically valuable compounds as well as compounds that are toxic, carcinogenic, and/or contributors to fungal pathogenesis. It is consequently important to understand the regulation of fungal secondary metabolism. McrA is a recently discovered transcription factor that negatively regulates fungal secondary metabolism. Deletion of mcrA (mcrA?), the gene encoding McrA, results in upregulation of many SMs and alters the expression of more than 1000 genes. One gene strongly upregulated by the deletion of mcrA is llmG, a putative methyl transferase related to LaeA, a major regulator of secondary metabolism. We artificially upregulated llmG by replacing its promoter with strong constitutive promoters in strains carrying either wild-type mcrA or mcrA?. Upregulation of llmG on various media resulted in increased production of the important toxin sterigmatocystin and compounds from at least six major SM pathways. llmG is, thus, a master SM regulator. mcrA? generally resulted in greater upregulation of SMs than upregulation of llmG, indicating that the full effects of mcrA on secondary metabolism involve genes in addition to llmG. However, the combination of mcrA? and upregulation of llmG generally resulted in greater compound production than mcrA? alone (in one case more than 460 times greater than the control). This result indicates that deletion of mcrA and/or upregulation of llmG can likely be combined with other strategies for eliciting SM production to greater levels than can be obtained with any single strategy.

SUBMITTER: Grau MF 

PROVIDER: S-EPMC7310610 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Overexpression of an LaeA-like Methyltransferase Upregulates Secondary Metabolite Production in <i>Aspergillus nidulans</i>.

Grau Michelle F MF   Entwistle Ruth R   Oakley C Elizabeth CE   Wang Clay C C CCC   Oakley Berl R BR  

ACS chemical biology 20190702 7


Fungal secondary metabolites (SMs) include medically valuable compounds as well as compounds that are toxic, carcinogenic, and/or contributors to fungal pathogenesis. It is consequently important to understand the regulation of fungal secondary metabolism. McrA is a recently discovered transcription factor that negatively regulates fungal secondary metabolism. Deletion of <i>mcrA</i> (<i>mcrA</i>Δ), the gene encoding McrA, results in upregulation of many SMs and alters the expression of more tha  ...[more]

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