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Regulation of fungal secondary metabolism

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TLDR
This Review describes the current understanding of the regulatory elements that modulate the transcription of genes involved in secondary metabolism and discusses how an improved knowledge of these regulatory elements will ultimately lead to a betterUnderstanding of the physiological and ecological functions of these important compounds.
Abstract
Fungi produce a multitude of low-molecular-mass compounds known as secondary metabolites, which have roles in a range of cellular processes such as transcription, development and intercellular communication. In addition, many of these compounds now have important applications, for instance, as antibiotics or immunosuppressants. Genome mining efforts indicate that the capability of fungi to produce secondary metabolites has been substantially underestimated because many of the fungal secondary metabolite biosynthesis gene clusters are silent under standard cultivation conditions. In this Review, I describe our current understanding of the regulatory elements that modulate the transcription of genes involved in secondary metabolism. I also discuss how an improved knowledge of these regulatory elements will ultimately lead to a better understanding of the physiological and ecological functions of these important compounds and will pave the way for a novel avenue to drug discovery through targeted activation of silent gene clusters.

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Citations
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One Juliet and four Romeos: VeA and its methyltransferases.

TL;DR: Interaction of VeA with at least four methyltransferase proteins indicates a molecular hub function for VeA that questions: Is there a VeA supercomplex or is VeA part of a highly dynamic cellular control network with many different partners?
Journal ArticleDOI

Discovery of microbial natural products by activation of silent biosynthetic gene clusters.

TL;DR: This Review discusses the strategies that have been developed in bacteria and fungi to identify and induce the expression of silent BGCs, and briefly summarize methods for the isolation and structural characterization of their metabolic products.
Journal ArticleDOI

Microbial interactions within the plant holobiont.

TL;DR: The fundamental role of microbe-microbe interactions (prokaryotes and micro-eukaryotes) for microbial community structure and plant health is discussed and a conceptual framework illustrating that interactions among microbiota members are critical for the establishment and the maintenance of host-microbial homeostasis is provided.

VelB/VeA/LaeA Complex CoordinatesLight Signal with Fungal Developmentand Secondary Metabolism

TL;DR: This work has identified the heterotrimeric velvet complex VelB/VeA/LaeA connecting light-responding developmental regulation and control of secondary metabolism in Aspergillus nidulans, which inhibits sexual reproduction as well as secondary metabolism.
Journal ArticleDOI

Fungal secondary metabolism: regulation, function and drug discovery.

TL;DR: New insights are discussed into the transcriptional and epigenetic regulation of BGCs and the ecological roles of fungal secondary metabolites in warfare, defence and development and avenues for the discovery of new fungal metabolites and current challenges in their identification are explored.
References
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Journal ArticleDOI

Bioactive microbial metabolites.

TL;DR: The short history, specific features and future prospects of research of microbial metabolites, including antibiotics and other bioactive metabolites, are summarized.
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antiSMASH: rapid identification, annotation and analysis of secondary metabolite biosynthesis gene clusters in bacterial and fungal genome sequences

TL;DR: This work presents the first comprehensive pipeline capable of identifying biosynthetic loci covering the whole range of known secondary metabolite compound classes, and integrates or cross-links all previously available secondary-metabolite specific gene analysis methods in one interactive view.
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Chromatin Modifications by Methylation and Ubiquitination: Implications in the Regulation of Gene Expression

TL;DR: The recent biochemical, molecular, cellular, and physiological functions of histone methylation and ubiquitination involved in the regulation of gene expression as determined by a combination of enzymological, structural, and genetic methodologies are highlighted.
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The Biosynthetic Logic of Polyketide Diversity

TL;DR: This review highlights recently unveiled biosynthetic mechanisms to generate highly diverse and complex molecules that lead to the large structural diversity of polyketides.
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LaeA, a Regulator of Secondary Metabolism in Aspergillus spp.

TL;DR: A novel Aspergillus nuclear protein, LaeA, is presented here as a global regulator of secondary metabolism in this genus, and strains show little difference in spore production compared to the wild type, indicating that the primary role of laeA is to regulate metabolic gene clusters.
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