How to Completely Squeeze a Fungus—Advanced Genome Mining Tools for Novel Bioactive Substances

Schüller, Andreas; Studt, Lena; Strauss, Joseph

doi:10.3390/pharmaceutics14091837

Cited by 11 publications

(8 citation statements)

References 459 publications

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“…As a result of the application of bioinformatics technologies, tens of thousands of BGCs have been found in fungal genomes, for most of which the products are still unknown [ 160 ]. Along with this, for all secondary metabolites from bacteria, fungi, and plants, fewer than two thousand corresponding BGCs have been experimentally characterized [ 220 , 221 ]. As a result, our knowledge of “wild” clusters (without characteristic core and tailoring enzymes) is much narrower than that of BGCs containing these elements.…”

Section: Biosynthetic Gene Clusters (Bgcs) For the Production Of Fung...mentioning

confidence: 99%

Fungal BGCs for Production of Secondary Metabolites: Main Types, Central Roles in Strain Improvement, and Regulation According to the Piano Principle

Zhgun

2023

IJMS

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Filamentous fungi are one of the most important producers of secondary metabolites. Some of them can havse a toxic effect on the human body, leading to diseases. On the other hand, they are widely used as pharmaceutically significant drugs, such as antibiotics, statins, and immunosuppressants. A single fungus species in response to various signals can produce 100 or more secondary metabolites. Such signaling is possible due to the coordinated regulation of several dozen biosynthetic gene clusters (BGCs), which are mosaically localized in different regions of fungal chromosomes. Their regulation includes several levels, from pathway-specific regulators, whose genes are localized inside BGCs, to global regulators of the cell (taking into account changes in pH, carbon consumption, etc.) and global regulators of secondary metabolism (affecting epigenetic changes driven by velvet family proteins, LaeA, etc.). In addition, various low-molecular-weight substances can have a mediating effect on such regulatory processes. This review is devoted to a critical analysis of the available data on the “turning on” and “off” of the biosynthesis of secondary metabolites in response to signals in filamentous fungi. To describe the ongoing processes, the model of “piano regulation” is proposed, whereby pressing a certain key (signal) leads to the extraction of a certain sound from the “musical instrument of the fungus cell”, which is expressed in the production of a specific secondary metabolite.

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Section: Biosynthetic Gene Clusters (Bgcs) For the Production Of Fung...mentioning

confidence: 99%

Fungal BGCs for Production of Secondary Metabolites: Main Types, Central Roles in Strain Improvement, and Regulation According to the Piano Principle

Zhgun

2023

IJMS

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“…Conventional methods can also be used to manipulate epigenetic remodelers for epigenome rewriting. Nevertheless, the CRISPR/Cas technology has greatly accelerated the advancement of epigenetic editing in bacteria [ 87 ], mammalian cells [ 88 ], plants [ 89 ], and fungi [ 90 ].…”

Section: Application Of Crispr/cas Systems In Fungal Genetic Engineeringmentioning

confidence: 99%

Advances and Challenges in CRISPR/Cas-Based Fungal Genome Engineering for Secondary Metabolite Production: A Review

Wang

Jin

et al. 2023

JoF

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Fungi represent an important source of bioactive secondary metabolites (SMs), which have wide applications in many fields, including medicine, agriculture, human health, and many other industries. The genes involved in SM biosynthesis are usually clustered adjacent to each other into a region known as a biosynthetic gene cluster (BGC). The recent advent of a diversity of genetic and genomic technologies has facilitated the identification of many cryptic or uncharacterized BGCs and their associated SMs. However, there are still many challenges that hamper the broader exploration of industrially important secondary metabolites. The recent advanced CRISPR/Cas system has revolutionized fungal genetic engineering and enabled the discovery of novel bioactive compounds. In this review, we firstly introduce fungal BGCs and their relationships with associated SMs, followed by a brief summary of the conventional strategies for fungal genetic engineering. Next, we introduce a range of state-of-the-art CRISPR/Cas-based tools that have been developed and review recent applications of these methods in fungi for research on the biosynthesis of SMs. Finally, the challenges and limitations of these CRISPR/Cas-based systems are discussed and directions for future research are proposed in order to expand their applications and improve efficiency for fungal genetic engineering.

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“…The regulatory networks of secondary metabolites and the epigenome have been linked in numerous studies. For example, the sterigmatocystin BGC of A. nidulans contains methylation marks on histone H3 residues during the active growth phase but is silent during the early growth phase ( Schüller et al., 2022 ). Although this study provides limited evidence that fungal SMs improve ecological fitness ( Alam et al., 2021 ), further research is essential to confirm similar phenomena.…”

Section: Fungal Secondary Metabolitesmentioning

confidence: 99%

The hidden power of secondary metabolites in plant-fungi interactions and sustainable phytoremediation

et al. 2022

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The global environment is dominated by various small exotic substances, known as secondary metabolites, produced by plants and microorganisms. Plants and fungi are particularly plentiful sources of these molecules, whose physiological functions, in many cases, remain a mystery. Fungal secondary metabolites (SM) are a diverse group of substances that exhibit a wide range of chemical properties and generally fall into one of four main family groups: Terpenoids, polyketides, non-ribosomal peptides, or a combination of the latter two. They are incredibly varied in their functions and are often related to the increased fitness of the respective fungus in its environment, often competing with other microbes or interacting with plant species. Several of these metabolites have essential roles in the biological control of plant diseases by various beneficial microorganisms used for crop protection and biofertilization worldwide. Besides direct toxic effects against phytopathogens, natural metabolites can promote root and shoot development and/or disease resistance by activating host systemic defenses. The ability of these microorganisms to synthesize and store biologically active metabolites that are a potent source of novel natural compounds beneficial for agriculture is becoming a top priority for SM fungi research. In this review, we will discuss fungal-plant secondary metabolites with antifungal properties and the role of signaling molecules in induced and acquired systemic resistance activities. Additionally, fungal secondary metabolites mimic plant promotion molecules such as auxins, gibberellins, and abscisic acid, which modulate plant growth under biotic stress. Moreover, we will present a new trend regarding phytoremediation applications using fungal secondary metabolites to achieve sustainable food production and microbial diversity in an eco-friendly environment.

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How to Completely Squeeze a Fungus—Advanced Genome Mining Tools for Novel Bioactive Substances

Cited by 11 publications

References 459 publications

Fungal BGCs for Production of Secondary Metabolites: Main Types, Central Roles in Strain Improvement, and Regulation According to the Piano Principle

Fungal BGCs for Production of Secondary Metabolites: Main Types, Central Roles in Strain Improvement, and Regulation According to the Piano Principle

Advances and Challenges in CRISPR/Cas-Based Fungal Genome Engineering for Secondary Metabolite Production: A Review

The hidden power of secondary metabolites in plant-fungi interactions and sustainable phytoremediation

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