NP MS Workflow: An Open-Source Software System to Empower Natural Product-Based Drug Discovery Using Untargeted Metabolomics.

Natural products (or specialized metabolites) are historically the main source of new drugs. However, the current drug discovery pipelines require miniaturization and speeds that are incompatible with traditional natural product research methods, especially in the early stages of the research. This article introduces the NP MS Workflow, a robust open-source software system for liquid chromatography-tandem mass spectrometry (LC-MS/MS) untargeted metabolomic data processing and analysis, designed to rank bioactive natural products directly from complex mixtures of compounds, such as bioactive biota samples.

Mass Spectrometry Analysis Reveals Lipids Induced by Oxidative Stress in Extracellular Vesicles.

is a commensal fungus in healthy humans that causes infection in immunocompromised individuals through the secretion of several virulence factors. The successful establishment of infection is owing to elaborate strategies to cope with defensive molecules secreted by the host, including responses toward oxidative stress. Extracellular vesicle (EV) release is considered an alternative to the biomolecule secretory mechanism that favors fungal interactions with the host cells.

The Histone Deacetylase Clr3 Regulates Secondary Metabolite Production and Tolerance to Oxidative Stress.

Most of the biosynthetic gene clusters (BGCs) found in microbes are silent under standard laboratory cultivation conditions due to the lack of expression triggering stimuli, representing a considerable drawback in drug discovery. To access the full biosynthetic potential, studies towards the activation of cryptic BGCs are essential. Histone acetylation status is an important regulator of chromatin structure, which impacts cell physiology and the expression of BGCs.

Heterogeneity in the transcriptional response of the human pathogen Aspergillus fumigatus to the antifungal agent caspofungin.

Aspergillus fumigatus is the main causative agent of invasive pulmonary aspergillosis (IPA), a severe disease that affects immunosuppressed patients worldwide. The fungistatic drug caspofungin (CSP) is the second line of therapy against IPA but has increasingly been used against clinical strains that are resistant to azoles, the first line antifungal therapy. In high concentrations, CSP induces a tolerance phenotype with partial reestablishment of fungal growth called CSP paradoxical effect (CPE), resulting from a change in the composition of the cell wall.

Evaluation of antimicrobial and antiproliferative activities of Actinobacteria isolated from the saline lagoons of northwestern Peru.

Extreme environments Morrope and Bayovar Salt lagoons, several ecosystems and microhabitats remain unexplored, and little is known about the diversity of Actinobacteria. We suggest that the endemic bacteria present in this extreme environment is a source of active molecules with anticancer, antimicrobial, and antiparasitic properties. Using phenotypic and genotypic characterization techniques, including 16S rRNA sequencing, we identified these bacteria as members of the genera Streptomyces, Pseudonocardia, Staphylococcus, Bacillus, and Pseudomonas.

Aspergillus fumigatus Acetate Utilization Impacts Virulence Traits and Pathogenicity.

Aspergillus fumigatus is a major opportunistic fungal pathogen of immunocompromised and immunocompetent hosts. To successfully establish an infection, A. fumigatus needs to use host carbon sources, such as acetate, present in the body fluids and peripheral tissues.

Açai ( Mart.) Seed Extract Induces ROS Production and Cell Death in MCF-7 Breast Cancer Cell Line.

Mart. (açai) is a native palm from the Amazon region. There are various chemical constituents of açai with bioactive properties.

Phytotoxic Tryptoquialanines Produced by Are Exported in Extracellular Vesicles.

is the most aggressive pathogen of citrus fruits. Tryptoquialanines are major indole alkaloids produced by It is unknown if tryptoquialanines are involved in the damage of citrus fruits caused by To investigate the pathogenic roles of tryptoquialanines, we initially asked if tryptoquialanines could affect the germination of seeds. Exposure of the citrus seeds to tryptoquialanine A resulted in a complete inhibition of germination and an altered metabolic response.

Exploring the interaction between citrus flavonoids and phytopathogenic fungi through enzymatic activities.

Flavonoids are involved in citrus defense against phytopathogens. In this study, we applied in vitro biocatalysis assays using the flavanones glycosides hesperidin and naringin to explore the enzymatic activities involved in such interaction. The main enzymatic activity observed was the hydrolysis catalyzed by fungi naringinases and hesperidinases.

Aspergillus fumigatus Transcription Factors Involved in the Caspofungin Paradoxical Effect.

is the leading cause of pulmonary fungal diseases. Azoles have been used for many years as the main antifungal agents to treat and prevent invasive aspergillosis. However, in the last 10 years there have been several reports of azole resistance in and new strategies are needed to combat invasive aspergillosis.

Anti-Estrogenic Activity of Guajadial Fraction, from Guava Leaves ( L.).

The research of natural products has allowed for the discovery of biologically relevant compounds inspired by plant secondary metabolites, which contributes to the development of many chemotherapeutic drugs used in cancer treatment. leaves present a diverse phytochemical composition including flavonoids, phenolics, meroterpenoids, and triterpenes as the major bioactive constituents. Guajadial, a caryophyllene-based meroterpenoid, has been studied for potential anticancer effects tested in tumor cells and animal experimental models.

Antifungal potential of secondary metabolites involved in the interaction between citrus pathogens.

Numerous postharvest diseases have been reported that cause substantial losses of citrus fruits worldwide. Penicillium digitatum is responsible for up to 90% of production losses, and represent a problem for worldwide economy. In order to control phytopathogens, chemical fungicides have been extensively used.

Biological Control of Citrus Postharvest Phytopathogens.

Citrus are vulnerable to the postharvest decay caused by , , and , which are responsible for the green mold, blue mold, and sour rot post-harvest disease, respectively. The widespread economic losses in citriculture caused by these phytopathogens are minimized with the use of synthetic fungicides such as imazalil, thiabendazole, pyrimethanil, and fludioxonil, which are mainly employed as control agents and may have harmful effects on human health and environment. To date, numerous non-chemical postharvest treatments have been investigated for the control of these pathogens.

Determination of tryptoquialanines A and C produced by Penicillium digitatum in oranges: Are we safe?

A method was developed and validated for determination of tryptoquialanines A and C in orange samples on epicarp (exterior peel), mesocarp (white peel), and endocarp (fruit juice) based on QuEChERS extraction and LC-MS/MS analysis. The method showed an excellent linearity over a range of 5-400 μg kg, with r ≥ 0.998.

Monitoring indole alkaloid production by Penicillium digitatum during infection process in citrus by Mass Spectrometry Imaging and molecular networking.

Green mold, caused by Penicillium digitatum, is the most destructive post-harvest disease in citrus. Secondary metabolites produced by fungal phytopathogens have been associated with toxicity to their respective host through the interaction with a wide range of cell targets. Natural products have also been described as important molecules for biocontrol and competition in their respective environment.

Penicillium digitatum infection mechanisms in citrus: What do we know so far?

Penicillium digitatum is the major source of postharvest decay in citrus fruits worldwide. This fungus shows a limited host range, being able to infect mainly mature fruit belonging to the Rutaceae family. This highly specific host interaction has attracted the interest of the scientific community.

Monoamine oxidase and transaminase screening: biotransformation of 2-methyl-6-alkylpiperidines by Neopestalotiopsis sp. CBMAI 2030.

High-throughput screening detected transaminases (TAs) and monoamine oxidases (MAOs) in fungi by applying a fluorogenic probe. Strains F026, F037, F041, F053, and F057 showed the highest enzymatic conversions (31, 60, 30, 40, and 32%, respectively) and where evaluated for their ability to transform piperidines. Strain F053 (Neopestalotiopsis sp.