Publications by authors named "Anelize Bauermeister"

23 Publications

  • Page 1 of 1

Mass spectrometry-based metabolomics in microbiome investigations.

Nat Rev Microbiol 2021 Sep 22. Epub 2021 Sep 22.

Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, San Diego, CA, USA.

Microbiotas are a malleable part of ecosystems, including the human ecosystem. Microorganisms affect not only the chemistry of their specific niche, such as the human gut, but also the chemistry of distant environments, such as other parts of the body. Mass spectrometry-based metabolomics is one of the key technologies to detect and identify the small molecules produced by the human microbiota, and to understand the functional role of these microbial metabolites. This Review provides a foundational introduction to common forms of untargeted mass spectrometry and the types of data that can be obtained in the context of microbiome analysis. Data analysis remains an obstacle; therefore, the emphasis is placed on data analysis approaches and integrative analysis, including the integration of microbiome sequencing data.
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http://dx.doi.org/10.1038/s41579-021-00621-9DOI Listing
September 2021

Quick-start infrastructure for untargeted metabolomics analysis in GNPS.

Nat Metab 2021 07;3(7):880-882

Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.

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http://dx.doi.org/10.1038/s42255-021-00429-0DOI Listing
July 2021

Ion identity molecular networking for mass spectrometry-based metabolomics in the GNPS environment.

Nat Commun 2021 06 22;12(1):3832. Epub 2021 Jun 22.

Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, OR, USA.

Molecular networking connects mass spectra of molecules based on the similarity of their fragmentation patterns. However, during ionization, molecules commonly form multiple ion species with different fragmentation behavior. As a result, the fragmentation spectra of these ion species often remain unconnected in tandem mass spectrometry-based molecular networks, leading to redundant and disconnected sub-networks of the same compound classes. To overcome this bottleneck, we develop Ion Identity Molecular Networking (IIMN) that integrates chromatographic peak shape correlation analysis into molecular networks to connect and collapse different ion species of the same molecule. The new feature relationships improve network connectivity for structurally related molecules, can be used to reveal unknown ion-ligand complexes, enhance annotation within molecular networks, and facilitate the expansion of spectral reference libraries. IIMN is integrated into various open source feature finding tools and the GNPS environment. Moreover, IIMN-based spectral libraries with a broad coverage of ion species are publicly available.
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http://dx.doi.org/10.1038/s41467-021-23953-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219731PMC
June 2021

Metabolomic study of marine Streptomyces sp.: Secondary metabolites and the production of potential anticancer compounds.

PLoS One 2020 21;15(12):e0244385. Epub 2020 Dec 21.

Departamento de Botânica, Instituto de Biociências, Universidade de São Paulo, São Paulo, São Paulo, Brazil.

Resorting to a One Strain Many Compounds (OSMAC) approach, the marine Streptomyces sp. BRB081 strain was grown in six different media settings over 1, 2, 3 or 7 days. Extractions of mycelium and broth were conducted separately for each media and cultivation period by sonication using methanol/acetone 1:1 and agitation with ethyl acetate, respectively. All methanol/acetone and ethyl acetate crude extracts were analysed by HPLC-MS/MS and data treatment was performed through GNPS platform using MZmine 2 software. In parallel, the genome was sequenced, assembled and mined to search for biosynthetic gene clusters (BGC) of secondary metabolites using the AntiSMASH 5.0 software. Spectral library search tool allowed the annotation of desferrioxamines, fatty acid amides, diketopiperazines, xanthurenic acid and, remarkably, the cyclic octapeptides surugamides. Molecular network analysis allowed the observation of the surugamides cluster, where surugamide A and the protonated molecule corresponding to the B-E isomers, as well as two potentially new analogues, were detected. Data treatment through MZmine 2 software allowed to distinguish that the largest amount of surugamides was obtained by cultivating BRB081 in SCB medium during 7 days and extraction of culture broth. Using the same data treatment, a chemical barcode was created for easy visualization and comparison of the metabolites produced overtime in all media. By genome mining of BRB081 four regions of biosynthetic gene clusters of secondary metabolites were detected supporting the metabolic data. Cytotoxic evaluation of all crude extracts using MTT assay revealed the highest bioactivity was also observed for extracts obtained in the optimal conditions as those for surugamides production, suggesting these to be the main active compounds herein. This method allowed the identification of compounds in the crude extracts and guided the selection of best conditions for production of bioactive compounds.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244385PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751980PMC
March 2021

Can Statistical Evaluation Tools for Chromatographic Method Development Assist in the Natural Products Workflow? A Case Study on Selected Species of the Plant Family Malpighiaceae.

J Nat Prod 2020 11 16;83(11):3239-3249. Epub 2020 Nov 16.

NuBBE, Department of Biochemistry and Organic Chemistry, Institute of Chemistry, São Paulo State University (UNESP), 14800-901, Araraquara, SP Brazil.

Proper chromatographic methods may reduce the challenges inherent in analyzing natural product extracts, especially when utilizing hyphenated detection techniques involving mass spectrometry. As there are many variations one can introduce during chromatographic method development, this can become a daunting and time-consuming task. To reduce the number of runs and time needed, the use of instrumental automatization and commercial software to apply Quality by Design and statistical analysis automatically can be a valuable approach to investigate complex matrices. To evaluate this strategy in the natural products workflow, a mixture of nine species from the family Malpighiaceae was investigated. By this approach, the entire data collection and method development procedure (comprising screening, optimization, and robustness simulation) was accomplished in only 4 days, resulting in very low limits of detection and quantification. The analysis of the individual extracts also proved the efficiency of the use of a mixture of extracts for this workflow. Molecular networking and library searches were used to annotate a total of 61 compounds, including -glycosylated flavonoids, -glycosylated flavonoids, quinic/shikimic acid derivatives, sterols, and other phenols, which were efficiently separated by the method developed. These results support the potential of statistical tools for chromatographic method optimization as an efficient approach to reduce time and maximize resources, such as solvents, to get proper chromatographic conditions.
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http://dx.doi.org/10.1021/acs.jnatprod.0c00495DOI Listing
November 2020

Anticancer Potential of Compounds from the Brazilian Blue Amazon.

Planta Med 2021 Feb 3;87(1-02):49-70. Epub 2020 Nov 3.

Departamento de Farmacologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brazil.

"Blue Amazon" is used to designate the Brazilian Economic Exclusive Zone, which covers an area comparable in size to that of its counterpart. Indeed, Brazil flaunts a coastline spanning 8000 km through tropical and temperate regions and hosting part of the organisms accredited for the country's megadiversity status. Still, biodiversity may be expressed at different scales of organization; besides species inventory, genetic characteristics of living beings and metabolic expression of their genes meet some of these other layers. These metabolites produced by terrestrial creatures traditionally and lately added to by those from marine organisms are recognized for their pharmaceutical value, since over 50% of small molecule-based medicines are related to natural products. Nonetheless, Brazil gives a modest contribution to the field of pharmacology and even less when considering marine pharmacology, which still lacks comprehensive in-depth assessments toward the bioactivity of marine compounds so far. Therefore, this review examined the last 40 years of Brazilian natural products research, focusing on molecules that evidenced anticancer potential-which represents ~ 15% of marine natural products isolated from Brazilian species. This review discusses the most promising compounds isolated from sponges, cnidarians, ascidians, and microbes in terms of their molecular targets and mechanisms of action. Wrapping up, the review delivers an outlook on the challenges that stand against developing groundbreaking natural products research in Brazil and on a means of surpassing these matters.
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http://dx.doi.org/10.1055/a-1257-8402DOI Listing
February 2021

ReDU: a framework to find and reanalyze public mass spectrometry data.

Nat Methods 2020 09 17;17(9):901-904. Epub 2020 Aug 17.

Grupo de Investigación en Ciencias Biológicas y Bioprocesos (CIBIOP), Department of Biological Sciences, Universidad EAFIT, Medellín, Colombia.

We present ReDU ( https://redu.ucsd.edu/ ), a system for metadata capture of public mass spectrometry-based metabolomics data, with validated controlled vocabularies. Systematic capture of knowledge enables the reanalysis of public data and/or co-analysis of one's own data. ReDU enables multiple types of analyses, including finding chemicals and associated metadata, comparing the shared and different chemicals between groups of samples, and metadata-filtered, repository-scale molecular networking.
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http://dx.doi.org/10.1038/s41592-020-0916-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968862PMC
September 2020

Linking genomics and metabolomics to chart specialized metabolic diversity.

Chem Soc Rev 2020 Jun 12;49(11):3297-3314. Epub 2020 May 12.

Bioinformatics Group, Wageningen University, Wageningen, The Netherlands.

Microbial and plant specialized metabolites constitute an immense chemical diversity, and play key roles in mediating ecological interactions between organisms. Also referred to as natural products, they have been widely applied in medicine, agriculture, cosmetic and food industries. Traditionally, the main discovery strategies have centered around the use of activity-guided fractionation of metabolite extracts. Increasingly, omics data is being used to complement this, as it has the potential to reduce rediscovery rates, guide experimental work towards the most promising metabolites, and identify enzymatic pathways that enable their biosynthetic production. In recent years, genomic and metabolomic analyses of specialized metabolic diversity have been scaled up to study thousands of samples simultaneously. Here, we survey data analysis technologies that facilitate the effective exploration of large genomic and metabolomic datasets, and discuss various emerging strategies to integrate these two types of omics data in order to further accelerate discovery.
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http://dx.doi.org/10.1039/d0cs00162gDOI Listing
June 2020

Targeting the Oncogenic TBX2 Transcription Factor With Chromomycins.

Front Chem 2020 3;8:110. Epub 2020 Mar 3.

Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.

The TBX2 transcription factor plays critical roles during embryonic development and it is overexpressed in several cancers, where it contributes to key oncogenic processes including the promotion of proliferation and bypass of senescence. Importantly, based on compelling biological evidences, TBX2 has been considered as a potential target for new anticancer therapies. There has therefore been a substantial interest to identify molecules with TBX2-modulatory activity, but no such substance has been found to date. Here, we adopt a targeted approach based on a reverse-affinity procedure to identify the ability of chromomycins A (CA) and A (CA) to interact with TBX2. Briefly, a TBX2-DNA-binding domain recombinant protein was N-terminally linked to a resin, which in turn, was incubated with either CA or CA. After elution, bound material was analyzed by UPLC-MS and CA was recovered from TBX2-loaded resins. To confirm and quantify the affinity (K) between the compounds and TBX2, microscale thermophoresis analysis was performed. CA and CA modified the thermophoretic behavior of TBX2, with a K in micromolar range. To begin to understand whether these compounds exerted their anti-cancer activity through binding TBX2, we next analyzed their cytotoxicity in TBX2 expressing breast carcinoma, melanoma and rhabdomyosarcoma cells. The results show that CA was consistently more potent than CA in all tested cell lines with IC values in the nM range. Of the cancer cell types tested, the melanoma cells were most sensitive. The knockdown of TBX2 in 501mel melanoma cells increased their sensitivity to CA by up to 5 times. Furthermore, inducible expression of TBX2 in 501mel cells genetically engineered to express TBX2 in the presence of doxycycline, were less sensitive to CA than the control cells. Together, the data presented in this study suggest that, in addition to its already recognized DNA-binding properties, CA may be binding the transcription factor TBX2, and it can contribute to its cytotoxic activity.
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http://dx.doi.org/10.3389/fchem.2020.00110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7062867PMC
March 2020

Marine Bacteria from Rocas Atoll as a Rich Source of Pharmacologically Active Compounds.

Mar Drugs 2019 Nov 28;17(12). Epub 2019 Nov 28.

Departamento de Farmacologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, 05508-900 São Paulo/SP, Brazil.

Rocas Atoll is a unique environment in the equatorial Atlantic Ocean, hosting a large number of endemic species, however, studies on the chemical diversity emerging from this biota are rather scarce. Therefore, the present work aims to assess the metabolomic diversity and pharmacological potential of the microbiota from Rocas Atoll. A total of 76 bacteria were isolated and cultured in liquid culture media to obtain crude extracts. About one third (34%) of these extracts were recognized as cytotoxic against human colon adenocarcinoma HCT-116 cell line. 16S rRNA gene sequencing analyses revealed that the bacteria producing cytotoxic extracts were mainly from the Actinobacteria phylum, including , , , and genera, and in a smaller proportion from Firmicutes phylum (). The search in the spectral library in GNPS (Global Natural Products Social Molecular Networking) unveiled a high chemodiversity being produced by these bacteria, including rifamycins, antimycins, desferrioxamines, ferrioxamines, surfactins, surugamides, staurosporines, and saliniketals, along with several unidentified compounds. Using an original approach, molecular networking successfully highlighted groups of compounds responsible for the cytotoxicity of crude extracts. Application of DEREPLICATOR+ (GNPS) allowed the annotation of macrolide novonestimycin derivatives as the cytotoxic compounds existing in the extracts produced by BRB-298 and BRB-302. Overall, these results highlighted the pharmacological potential of bacteria from this singular atoll.
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http://dx.doi.org/10.3390/md17120671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949966PMC
November 2019

Enriching cancer pharmacology with drugs of marine origin.

Br J Pharmacol 2020 01 23;177(1):3-27. Epub 2019 Dec 23.

Departamento de Farmacologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brasil.

Marine natural products have proven, over the last half-century, to be effective biological modulators. These molecules have revealed new targets for cancer therapy as well as dissimilar modes of action within typical classes of drugs. In this scenario, innovation from marine-based pharmaceuticals has helped advance cancer chemotherapy in many aspects, as most of these are designated as first-in-class drugs. Here, by examining the path from discovery to development of clinically approved drugs of marine origin for cancer treatment-cytarabine (Cytosar-U®), trabectedin (Yondelis®), eribulin (Halaven®), brentuximab vedotin (Adcetris®), and plitidepsin (Aplidin®)- together with those in late clinical trial phases-lurbinectedin, plinabulin, marizomib, and plocabulin-the present review offers a critical analysis of the contributions given by these new compounds to cancer pharmacotherapy.
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http://dx.doi.org/10.1111/bph.14876DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6976878PMC
January 2020

Pradimicin-IRD exhibits antineoplastic effects by inducing DNA damage in colon cancer cells.

Biochem Pharmacol 2019 10 19;168:38-47. Epub 2019 Jun 19.

Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil. Electronic address:

DNA-damaging agents are widely used in cancer therapy; however, their use is limited by dose-related toxicities, as well as the development of drug resistance. Drug discovery is essential to overcome these limitations and offer novel therapeutic options. In a previous study by our research group, pradimicin-IRD-a new polycyclic antibiotic produced by the actinobacteria Amycolatopsis sp.-displayed antimicrobial and potential anticancer activities. In the present study, cytotoxic activity was further confirmed in a panel of five colon cancer, including those with mutation in TP53 and KRAS, the most common ones observed in cancer colon patients. While all tested colon cancer cells were sensitive to pradimicin-IRD treatment with IC in micromolar range, non-tumor fibroblasts were significantly less sensitive (p < 0.05). The cellular and molecular mechanism of action of pradimicin-IRD was then investigated in the colorectal cancer cell line HCT 116. Pradimicin-IRD presented antitumor effects occurring after at least 6 h of exposure. Pradimicin-IRD induced statistically significant DNA damage (γH2AX and p21), apoptosis (PARP1 and caspase 3 cleavage) and cell cycle arrest (reduced Rb phosphorylation, cyclin A and cyclin B expression) markers. In accordance with these results, pradimicin-IRD increased cell populations in the subG and G/G phases of the cell cycle. Additionally, mass spectrometry analysis indicated that pradimicin-IRD interacted with the DNA double strand. In summary, pradimicin-IRD exhibits multiple antineoplastic activities-including DNA damage, cell cycle arrest, reduction of clonal growth and apoptosis-in the HCT 116 cell line. Furthermore, pradimicin-IRD displays a TP53-independent regulation of p21 expression in HCT 116 TP53, HT-29, SW480, and Caco-2 cells. This exploratory study identified novel targets for pradimicin-IRD and provided insights for its potential anticancer activity as a DNA-damaging agent.
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http://dx.doi.org/10.1016/j.bcp.2019.06.016DOI Listing
October 2019

Integrating Molecular Network and Culture Media Variation to Explore the Production of Bioactive Metabolites by A1SM3.

Mar Drugs 2019 Mar 27;17(4). Epub 2019 Mar 27.

Bioscience Doctoral Program, Grupo de Investigación en Bioprospección, Faculty of Engineering, Universidad de La Sabana, Campus Puente del Común, Km 7, Autopista Norte de Bogotá, 250001 Chía, Colombia.

A1SM3 strain was isolated from a sediment sample from Manaure Solar Saltern in La Guajira and the produced crude extracts have shown antibacterial activity against methicillin-resistant and cytotoxic activity against human lung cell line. Thus, the aim of this research was to identify the main compound responsible for the biological activity observed and to systematically study how each carbon and nitrogen source in the growth media, and variation of the salinity, affect its production. For the characterization of the bioactive metabolites, 15 fractions obtained from A1SM3 crude extract were analyzed by HPLC-MS/MS and their activity was established. The bioactive fractions were dereplicated with Antibase and Marinlit databases, which combined with nuclear magnetic resonance (NMR) spectra and fragmentation by MS/MS, led to the identification of 2,2-di(3-indolyl)-3-indolone (isotrisindoline), an indole-derivative antibiotic, previously isolated from marine organisms. The influence of the variations of the culture media in isotrisindoline production was established by molecular network and MZmine showing that the media containing starch and peptone at 7% NaCl was the best culture media to produce it. Also, polyhydroxybutyrates (PHB) identification was established by MS/MS mainly in casamino acids media, contributing to the first report on PHB production by this strain.
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http://dx.doi.org/10.3390/md17040196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6520778PMC
March 2019

Evaluation of anti-HSV-1 activity and toxicity of hydroethanolic extract of Tanacetum parthenium (L.) Sch.Bip. (Asteraceae).

Phytomedicine 2019 Mar 13;55:249-254. Epub 2018 Aug 13.

Department of Basic Health Sciences, State University of Maringá, Maringá, Paraná, Brazil. Electronic address:

Background: Herpes simplex type 1 (HSV-1) is widely distributed throughout the world's population. The virus spreads through direct contact with an infected individual. After primary infection, the virus remains in a latent state, and the recurrence of herpetic lesions is common. Standard treatment is performed with nucleoside analogues, but the selection of resistant strains have occurred, thus requiring the continual search for new antiviral agents. Plant extracts, fractions, and isolated compounds are a good source for studying possible antiviral compounds.

Hypothesis: Among plants with antiviral activity, the crude extract of aerial parts of Tanacetum parthenium (L.) Sch.Bip. (Asteraceae) have previously shown to inhibit HSV-1 infection in vitro.

Methods: The present study investigated the chemical composition of a crude hydroethanolic extract (CHE) of T. parthenium, and in vivo safety and therapeutic efficacy against HSV-1 infection.

Results: Liquid chromatography-mass spectrometry showed that the CHE was composed of phenolic acids (chlorogenic acids) and sesquiterpene lactones (parthenolide). Acute and subchronic toxicity and genotoxicity tests in vivo showed that oral CHE administration did not result in signs of toxicity, with no genotoxic potential. The CHE was also safe for topical administration, in which no irritation of the epidermis was observed in treated animals. Tests of topical and oral therapeutic efficacy showed that the CHE was effective against HSV-1 infection. Topical administration was the most effective, the results for which were comparable to acyclovir.

Conclusion: These findings indicate that the CHE from aerial parts of Tanacetum parthenium has in vivo anti-HSV-1 activity and is safe for oral and topical application.
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http://dx.doi.org/10.1016/j.phymed.2018.06.040DOI Listing
March 2019

Intra-clade metabolomic profiling of MAR4 Streptomyces from the Macaronesia Atlantic region reveals a source of anti-biofilm metabolites.

Environ Microbiol 2019 03 22;21(3):1099-1112. Epub 2019 Feb 22.

LAQV-REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa 2829-516, Caparica, Portugal.

The search for new and effective strategies to reduce bacterial biofilm formation is of utmost importance as bacterial resistance to antibiotics continues to emerge. The use of anti-biofilm agents that can disrupt recalcitrant bacterial communities can be an advantageous alternative to antimicrobials, as their use does not lead to the development of resistance mechanisms. Six MAR4 Streptomyces strains isolated from the Madeira Archipelago, at the unexplored Macaronesia Atlantic ecoregion, were used to study the chemical diversity of produced hybrid isoprenoids. These marine actinomycetes were investigated by analysing their crude extracts using LC-MS/MS and their metabolomic profiles were compared using multivariate statistical analysis (principal component analysis), showing a separation trend closely related to their phylogeny. Molecular networking unveiled the presence of a class of metabolites not previously described from MAR4 strains and new chemical derivatives belonging to the napyradiomycin and marinone classes. Furthermore, these MAR4 strains produce metabolites that inhibit biofilm formation of Staphylococcus aureus and Marinobacter hydrocarbonoclasticus. The anti-biofilm activity of napyradiomycin SF2415B3 (1) against S. aureus was confirmed.
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http://dx.doi.org/10.1111/1462-2920.14529DOI Listing
March 2019

Metabolomic Fingerprinting of From Atlantic Oceanic Islands.

Front Microbiol 2018 11;9:3021. Epub 2018 Dec 11.

Departamento de Farmacologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil.

(Micromonosporaceae) is an obligate marine bacterium genus consisting of three species that share over 99% 16S rRNA identity. The genome and biosynthetic pathways of the members of this genus have been widely investigated due to their production of species-specific metabolites. However, despite the species' high genetic similarity, site-specific secondary metabolic gene clusters have been found in strains collected at different locations. Therefore, exploring the metabolic expression of recovered from different sites may furnish insights into their environmental adaptation or their chemical communication and, further, may lead to the discovery of new natural products. We describe the first occurrence of strains in sediments from the Saint Peter and Saint Paul Archipelago (a collection of islets in Brazil) in the Atlantic Ocean, and we investigate the metabolic profiles of these strains by employing mass-spectrometry-based metabolomic approaches, including molecular networking from the Global Natural Products Social Molecular Networking platform. Furthermore, we analyze data from strains recovered from sediments from the Madeira Archipelago (Portugal, Macaronesia) in order to provide a wider metabolomic investigation of strains from the Atlantic Oceanic islands. Overall, our study evidences a broader geographic influence on the secondary metabolism of than was previously proposed. Still, some biosynthetic gene clusters, such as those corresponding to typical chemical signatures of , like saliniketals and rifamycins, are highly conserved among the assessed strains.
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http://dx.doi.org/10.3389/fmicb.2018.03021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6297358PMC
December 2018

Pradimicin-IRD from sp. IRD-009 and its antimicrobial and cytotoxic activities.

Nat Prod Res 2019 Jun 16;33(12):1713-1720. Epub 2018 Feb 16.

a Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto , Universidade de São Paulo , Ribeirão Preto , Brazil.

A new polycyclic antibiotic, pradimicin-IRD, was isolated from actinobacteria sp. IRD-009 recovered from soil of Brazilian rainforest undergoing restoration area. This molecule is the major compound produced in solid culture media. The new compound was detected by a focused method of precursor ion (high-performance liquid chromatography coupled to tandem mass spectrometer) developed previously to identify unusual aminoglycosyl sugar moieties. The compound was isolated and its structure was, therefore, elucidated by high-resolution mass spectrometry, and 1D and 2D nuclear magnetic resonance experiments. Pradimicin-IRD displayed potential antimicrobial activity against (MIC 3.1 μg/mL), (MIC 3.1 μg/mL) and (MIC 3.1 μg/mL), and also cytotoxicity against tumour and non-tumour cell lines with IC values ranging from 0.8 μM in HCT-116 colon carcinoma cells to 2.7 μM in MM 200 melanoma cells. Particularly, these biological properties are described for the first time for this chemical class.
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http://dx.doi.org/10.1080/14786419.2018.1434639DOI Listing
June 2019

Fragmentation pathway and structural characterization of new glycosylated phenolic derivatives from Eremanthus glomerulatus Less (Asteraceae) by electrospray ionization tandem mass spectrometry.

J Mass Spectrom 2017 Nov;52(11):783-787

Núcleo de Pesquisa em Produtos Naturais e Sintéticos (NPPNS), Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Avenida do Café s/n, 14040-903, Ribeirão Preto, SP, Brazil.

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http://dx.doi.org/10.1002/jms.3982DOI Listing
November 2017

A Simple Defined Medium for the Production of True Diketopiperazines in Xylella fastidiosa and Their Identification by Ultra-Fast Liquid Chromatography-Electrospray Ionization Ion Trap Mass Spectrometry.

Molecules 2017 Jun 13;22(6). Epub 2017 Jun 13.

Centro APTA Citros Sylvio Moreira, Instituto Agronômico, CP 04, 13490-970 Cordeirópolis-SP, Brazil.

Diketopiperazines can be generated by non-enzymatic cyclization of linear dipeptides at extreme temperature or pH, and the complex medium used to culture bacteria and fungi including phytone peptone and trypticase peptone, can also produce cyclic peptides by heat sterilization. As a result, it is not always clear if many diketopiperazines reported in the literature are artifacts formed by the different complex media used in microorganism growth. An ideal method for analysis of these compounds should identify whether they are either synthesized de novo from the products of primary metabolism and deliver true diketopiperazines. A simple defined medium ( medium or XFM) containing a single carbon source and no preformed amino acids has emerged as a method with a particularly high potential for the grown of and to produce genuine natural products. In this work, we identified a range of diketopiperazines from 9a5c growth in XFM, using Ultra-Fast Liquid Chromatography coupled with mass spectrometry. Diketopiperazines are reported for the first time from , which is responsible for citrus variegated chlorosis. We also report here fatty acids from , which were not biologically active as diffusible signals, and the role of diketopiperazines in signal transduction still remains unknown.
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http://dx.doi.org/10.3390/molecules22060985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6152636PMC
June 2017

In Vitro Metabolism Evaluation of the Ergot Alkaloid Dihydroergotamine: Application of Microsomal and Biomimetic Oxidative Model.

Planta Med 2016 Oct 2;82(15):1368-1373. Epub 2016 Aug 2.

Núcleo de Pesquisa em Produtos Naturais e Sintéticos (NPPNS), Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.

Dihydroergotamine is a semisynthetic natural product derived from ergotamine, an ergot alkaloid. It is used to treat migraines, a neurological disease characterized by recurrent moderate to severe headaches. In this work, the metabolism of dihydroergotamine was evaluated in a biomimetic phase I reaction, aiming to verify all possible formed metabolites. Dihydroergotamine was submitted to an metabolism assay using rat liver microsomes, and the metabolites were analyzed by HPLC-MS/MS. The biomimetic reactions were performed with Jacobsen catalyst for scaling up production of oxidized metabolites. Two hydroxylated metabolites were isolated and characterized by MS/MS and H NMR analysis.
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http://dx.doi.org/10.1055/s-0042-111732DOI Listing
October 2016

Mass spectrometric approaches for the identification of anthracycline analogs produced by actinobacteria.

J Mass Spectrom 2016 Jun;51(6):437-45

Mass Spectrometry Applied to Natural Products Laboratory, Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, CEP: 14040-901, Ribeirão Preto, SP, Brazil.

Anthracyclines are a well-known chemical class produced by actinobacteria used effectively in cancer treatment; however, these compounds are usually produced in few amounts because of being toxic against their producers. In this work, we successfully explored the mass spectrometry versatility to detect 18 anthracyclines in microbial crude extract. From collision-induced dissociation and nuclear magnetic resonance spectra, we proposed structures for five new and identified three more anthracyclines already described in the literature, nocardicyclins A and B and nothramicin. One new compound 8 (4-[4-(dimethylamino)-5-hydroxy-4,6-dimethyloxan-2-yl]oxy-2,5,7,12-tetrahydroxy-3,10-dimethoxy-2-methyl-3,4-dihydrotetracene-1,6,11-trione) was isolated and had its structure confirmed by (1) H nuclear magnetic resonance. The anthracyclines identified in this work show an interesting aminoglycoside, poorly found in natural products, 3-methyl-rhodosamine and derivatives. This fact encouraged to develop a focused method to identify compounds with aminoglycosides (rhodosamine, m/z 158; 3-methyl-rhodosamine, m/z 172; 4'-O-acethyl-3-C-methyl-rhodosamine, m/z 214). This method allowed the detection of four more anthracyclines. This focused method can also be applied in the search of these aminoglycosides in other microbial crude extracts. Additionally, it was observed that nocardicyclin A, nothramicin and compound 8 were able to interact to DNA through a DNA-binding study by mass spectrometry, showing its potential as anticancer drugs. Copyright © 2016 John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/jms.3772DOI Listing
June 2016

β-(1 → 3)-Glucanolytic yeasts from Brazilian grape microbiota: production and characterization of β-glucanolytic enzymes by Aureobasidium pullulans 1WA1 cultivated on fungal Mycelium.

J Agric Food Chem 2015 Jan;63(1):269-78

A total of 95 yeast strains were isolated from the microbiota of different grapes collected at vineyards in southern Brazil. The yeasts were screened for β-(1 → 3)-glucanases using a newly developed zymogram method that relies upon the appearance of clearance zones around growing colonies cultured on agar–botryosphaeran medium and also by submerged fermentation on nutrient medium containing botryosphaeran, a (1 → 3),(1 → 6)-β-d-glucan. Among 14 β-(1 → 3)-glucanase-positive yeasts identified, four strains produced the highest β-glucanolytic activities and were evaluated for enzyme production on cellobiose, botryosphaeran, and mycelial biomass from Botryosphaeria rhodina (MAMB-05). Yeast strain 1WA1 produced the highest β-(1 → 3)-glucanase and β-glucosidase activities and was identified by molecular characterization as Aureobasidium pullulans. The physicochemical properties of the crude β-glucanolytic enzyme preparation were characterized, and the preparation was used to hydrolyze several β-d-glucans (laminarin, botryosphaeran, lasiodiplodan, pustulan, and curdlan). The production and physicochemical properties of the β-glucanolytic preparation enable its potential applications in wine enology and production of prebiotics through hydrolysis of β-d-glucans.
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http://dx.doi.org/10.1021/jf504333hDOI Listing
January 2015
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