Classical and epigenetic approaches to metabolite diversification in filamentous fungi

Takahashi, Jacqueline A.; Teles, Ana; Bracarense, Adriana de Almeida Pinto; Gomes, Dhionne Corrêia

doi:10.1007/s11101-013-9305-5

Cited by 36 publications

(26 citation statements)

References 79 publications

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“…The one strain-many compounds (OSMAC) strategy [5] and chemical epigenetics methodology [6] have been widely used by microbial chemists to access cryptic secondary metabolites [7]. The ribosome engineering strategy [8] provided another simple way to activate silent pathways by introducing drug-resistance mutations in bacteria to discover new antibiotics [9].…”

Section: Introductionmentioning

confidence: 99%

Seven New and Two Known Lipopeptides as well as Five Known Polyketides: The Activated Production of Silent Metabolites in a Marine-Derived Fungus by Chemical Mutagenesis Strategy Using Diethyl Sulphate

Li²,

Cui

2014

Marine Drugs

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AD-2-1 is an antitumor fungal mutant obtained by diethyl sulfate mutagenesis of a marine-derived Penicillium purpurogenum G59. The G59 strain originally did not produce any metabolites with antitumor activities in MTT assays using K562 cells. Tracing newly produced metabolites under guidance of MTT assay and TLC analysis by direct comparison with control G59 extract, seven new (1–7) and two known (8–9) lipopeptides were isolated together with five known polyketides 10–14 from the extract of mutant AD-2-1. Structures of the seven new compounds including their absolute configurations were determined by spectroscopic and chemical evidences and named as penicimutalides A–G (1–7). Seven known compounds were identified as fellutamide B (8), fellutamide C (9), 1′-O-methylaverantin (10), averantin (11), averufin (12), nidurufin (13), and sterigmatocystin (14). In the MTT assay, 1–14 inhibited several human cancer cell lines to varying extents. All the bioassays and HPLC-photodiode array detector (PDAD)-UV and HPLC-electron spray ionization (ESI)-MS analyses demonstrated that the production of 1–14 in the mutant AD-2-1 was caused by the activated production of silent metabolites in the original G59 fungal strain. Present results provided additional examples for effectiveness of the chemical mutagenesis strategy using diethyl sulphate mutagenesis to discover new compounds by activating silent metabolites in fungal isolates.

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Section: Introductionmentioning

confidence: 99%

Seven New and Two Known Lipopeptides as well as Five Known Polyketides: The Activated Production of Silent Metabolites in a Marine-Derived Fungus by Chemical Mutagenesis Strategy Using Diethyl Sulphate

Li²,

Cui

2014

Marine Drugs

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“…), bearing an unprecedented terpenoid side chain and exhibiting high cytotoxicity against L‐929 mouse fibroblast cell lines (GI 50 10.6/11.4 μg/mL) . Exposing the fungus Aspergillus terreus to stress factors, such as different pH and temperature conditions, significantly influenced its metabolic profile, especially its production of antibacterial metabolites …”

Section: Novel Organisms and Manipulation Of Natural Metabolismmentioning

confidence: 99%

Strategies to diversify natural products for drug discovery

Lou

2017

Medicinal Research Reviews

215

130

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Natural product libraries contain specialized metabolites derived from plants, animals, and microorganisms that play a pivotal role in drug discovery due to their immense structural diversity and wide variety of biological activities. The strategies to greatly extend natural product scaffolds through available biological and chemical approaches offer unique opportunities to access a new series of natural product analogues, enabling the construction of diverse natural product-like libraries. The affordability of these structurally diverse molecules has been a crucial step in accelerating drug discovery. This review provides an overview of various approaches to exploit the diversity of compounds for natural product-based drug development, drawing upon a series of examples to illustrate each strategy.

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“…SM production by microbes is observed to vary with composition of culture media and culture conditions [22]. Hence culturing of microbes in diverse media is a classic approach [often termed as OSMAC (one strain many compounds)] to activate silent BGCs [23,24]. Alteration of other cultivation parameters, such as temperature, salinity, flask shapes and aeration have proved effective in triggering cryptic biosynthetic pathways in A. ochraceus [22].…”

Section: Triggering Microbial Silent Bgcsmentioning

confidence: 99%

Activation of Microbial Silent Gene Clusters: Genomics Driven Drug Discovery Approaches

Valayil¹

2016

Biochem Anal Biochem

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Microorganisms have provided mankind with a plethora of small molecule natural products ranging from industrial enzymes to therapeutic agents. Analyses of microbial genome sequences have revealed the presence of numerous 'silent' or 'cryptic' biosynthetic gene clusters (BGCs). Activation of these cryptic biosynthetic pathways can pave way to the discovery of novel bioactive secondary metabolites (SMs). This article summarizes various approaches employed to unlock the hidden biosynthetic potential of microbes and methods developed to study their silent gene products.

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Classical and epigenetic approaches to metabolite diversification in filamentous fungi

Cited by 36 publications

References 79 publications

Seven New and Two Known Lipopeptides as well as Five Known Polyketides: The Activated Production of Silent Metabolites in a Marine-Derived Fungus by Chemical Mutagenesis Strategy Using Diethyl Sulphate

Seven New and Two Known Lipopeptides as well as Five Known Polyketides: The Activated Production of Silent Metabolites in a Marine-Derived Fungus by Chemical Mutagenesis Strategy Using Diethyl Sulphate

Strategies to diversify natural products for drug discovery

Activation of Microbial Silent Gene Clusters: Genomics Driven Drug Discovery Approaches

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