Search

Your search keyword '"Mevers, Emily"' showing total 154 results
Start Over Author "Mevers, Emily"
154 results on '"Mevers, Emily"'

2. Lactiplantibacillus plantarum uses ecologically relevant, exogenous quinones for extracellular electron transfer.

Author

Stevens, Eric, Van Beeck, Wannes, Blackburn, Benjamin, Tejedor-Sanz, Sara, Carter, Mackenzie, Mevers, Emily, Ajo-Franklin, Caroline, Marco, Maria, and Rasmussen, Alycia

Subjects
cross-feeding, fermentation, lactic acid bacteria, oxidation-reduction, transcriptome
Abstract

While quinones are essential for respiratory microorganisms, their importance for microbes that rely on fermentation metabolism is not understood. This gap in knowledge hinders our understanding of anaerobic microbial habitats, such in mammalian digestive tracts and fermented foods. We show that Lactiplantibacillus plantarum, a model fermentative lactic acid bacteria species abundant in human, animal, and insect microbiomes and fermented foods, uses multiple exogenous, environmental quinones as electron shuttles for a hybrid metabolism involving EET. Interestingly, quinones both stimulate this metabolism as well as cause oxidative stress when extracellular electron acceptors are absent. We also found that quinone-producing, lactic acid bacteria species commonly enriched together with L. plantarum in food fermentations accelerate L. plantarum growth and medium acidification through a mainly quinone- and EET-dependent mechanism. Thus, our work provides evidence of quinone cross-feeding as a key ecological feature of anaerobic microbial habitats.

Published
2023

7. Canvass: A Crowd-Sourced, Natural-Product Screening Library for Exploring Biological Space.

Author

Kearney, Sara E, Zahoránszky-Kőhalmi, Gergely, Brimacombe, Kyle R, Henderson, Mark J, Lynch, Caitlin, Zhao, Tongan, Wan, Kanny K, Itkin, Zina, Dillon, Christopher, Shen, Min, Cheff, Dorian M, Lee, Tobie D, Bougie, Danielle, Cheng, Ken, Coussens, Nathan P, Dorjsuren, Dorjbal, Eastman, Richard T, Huang, Ruili, Iannotti, Michael J, Karavadhi, Surendra, Klumpp-Thomas, Carleen, Roth, Jacob S, Sakamuru, Srilatha, Sun, Wei, Titus, Steven A, Yasgar, Adam, Zhang, Ya-Qin, Zhao, Jinghua, Andrade, Rodrigo B, Brown, M Kevin, Burns, Noah Z, Cha, Jin K, Mevers, Emily E, Clardy, Jon, Clement, Jason A, Crooks, Peter A, Cuny, Gregory D, Ganor, Jake, Moreno, Jesus, Morrill, Lucas A, Picazo, Elias, Susick, Robert B, Garg, Neil K, Goess, Brian C, Grossman, Robert B, Hughes, Chambers C, Johnston, Jeffrey N, Joullie, Madeleine M, Kinghorn, A Douglas, Kingston, David GI, Krische, Michael J, Kwon, Ohyun, Maimone, Thomas J, Majumdar, Susruta, Maloney, Katherine N, Mohamed, Enas, Murphy, Brian T, Nagorny, Pavel, Olson, David E, Overman, Larry E, Brown, Lauren E, Snyder, John K, Porco, John A, Rivas, Fatima, Ross, Samir A, Sarpong, Richmond, Sharma, Indrajeet, Shaw, Jared T, Xu, Zhengren, Shen, Ben, Shi, Wei, Stephenson, Corey RJ, Verano, Alyssa L, Tan, Derek S, Tang, Yi, Taylor, Richard E, Thomson, Regan J, Vosburg, David A, Wu, Jimmy, Wuest, William M, Zakarian, Armen, Zhang, Yufeng, Ren, Tianjing, Zuo, Zhong, Inglese, James, Michael, Sam, Simeonov, Anton, Zheng, Wei, Shinn, Paul, Jadhav, Ajit, Boxer, Matthew B, Hall, Matthew D, Xia, Menghang, Guha, Rajarshi, and Rohde, Jason M

Subjects
Chemical Sciences
Abstract

Natural products and their derivatives continue to be wellsprings of nascent therapeutic potential. However, many laboratories have limited resources for biological evaluation, leaving their previously isolated or synthesized compounds largely or completely untested. To address this issue, the Canvass library of natural products was assembled, in collaboration with academic and industry researchers, for quantitative high-throughput screening (qHTS) across a diverse set of cell-based and biochemical assays. Characterization of the library in terms of physicochemical properties, structural diversity, and similarity to compounds in publicly available libraries indicates that the Canvass library contains many structural elements in common with approved drugs. The assay data generated were analyzed using a variety of quality control metrics, and the resultant assay profiles were explored using statistical methods, such as clustering and compound promiscuity analyses. Individual compounds were then sorted by structural class and activity profiles. Differential behavior based on these classifications, as well as noteworthy activities, are outlined herein. One such highlight is the activity of (-)-2(S)-cathafoline, which was found to stabilize calcium levels in the endoplasmic reticulum. The workflow described here illustrates a pilot effort to broadly survey the biological potential of natural products by utilizing the power of automation and high-throughput screening.

Published
2018

9. A Maldiisotopic Approach to Discover Natural Products: Cryptomaldamide, a Hybrid Tripeptide from the Marine Cyanobacterium Moorea producens

Author

Kinnel, Robin B, Esquenazi, Eduardo, Leao, Tiago, Moss, Nathan, Mevers, Emily, Pereira, Alban R, Monroe, Emily A, Korobeynikov, Anton, Murray, Thomas F, Sherman, David, Gerwick, Lena, Dorrestein, Pieter C, and Gerwick, William H

Subjects
Human Genome, Genetics, Biological Products, Computational Biology, Cyanobacteria, Magnetic Resonance Spectroscopy, Molecular Structure, Oligopeptides, Chemical Sciences, Biological Sciences, Medical and Health Sciences, Medicinal & Biomolecular Chemistry
Abstract

Genome sequencing of microorganisms has revealed a greatly increased capacity for natural products biosynthesis than was previously recognized from compound isolation efforts alone. Hence, new methods are needed for the discovery and description of this hidden secondary metabolite potential. Here we show that provision of heavy nitrogen 15N-nitrate to marine cyanobacterial cultures followed by single-filament MALDI analysis over a period of days was highly effective in identifying a new natural product with an exceptionally high nitrogen content. The compound, named cryptomaldamide, was subsequently isolated using MS to guide the purification process, and its structure determined by 2D NMR and other spectroscopic and chromatographic methods. Bioinformatic analysis of the draft genome sequence identified a 28.7 kB gene cluster that putatively encodes for cryptomaldamide biosynthesis. Notably, an amidinotransferase is proposed to initiate the biosynthetic process by transferring an amidino group from arginine to serine to produce the first residue to be incorporated by the hybrid NRPS-PKS pathway. The maldiisotopic approach presented here is thus demonstrated to provide an orthogonal method by which to discover novel chemical diversity from Nature.

Published
2017

21. Investigations into Bioactive Secondary Metabolites Produced by Marine Cyanobacteria /

Author

Mevers, Emily

Subjects
UCSD Dissertations, Academic Chemistry. (Discipline)
Abstract

Marine cyanobacteria are prolific producers of structurally intriguing and biologically important secondary metabolites, many of which are of mixed NRPS/PKS biosynthetic origins, and have a broad range of biological activity, including ion channel modulation, cancer cell toxicity, anti-parasitic, anti-bacterial, anti- inflammatory, brine shrimp toxicity, and molluscicidal. Presently, there is one clinically approved drug that is an analog of the cyanobacterial natural product, dolastatin 10, while there are several agents in clinical trial, including soblidotin and synthadotin, which are analogs of dolastatin 15 and 10, respectively. Additionally, others are currently undergoing preclinical evaluation as anti-cancer agents, including apratoxin F, curacin A, desmethoxymajusculamide C (DMMC) and somacystinamide. The primary research objective of the research herein was to isolate and elucidate the structures of biologically active secondary metabolites from tropical marine cyanobacteria. In total, fifteen novel compounds from either Oscillatoria or Moorea were isolated and characterized. These include thirteen highly modified peptides (veraguamides A-C and H-L, precarriebowmide, tasiamides C-E, and lyngbyabellin N) and two alkyl amides (parguerene and mooreamide). The planar structure elucidation of each of these metabolites involved the use of 2D NMR spectroscopy and mass spectrometry techniques, including a mass spectrometry based dereplication algorithm to deduce the planar structure of several of the modified peptides. Absolute stereochemical analysis involved many techniques, such as Marfey's analysis, semi-synthesis, ³J coupling constant analysis, circular dichroism, ¹³C NMR comparisions, NOE correlations, and chiral GCMS analysis. Many of these compounds were biologically evaluated with veraguamide A and lyngbyabellin N exhibiting cancer cell cytotoxicity [IC₅₀ = 141 nM (H-460) and IC₅₀ = 40.9 (HCT-116), respectively], and mooreamide exhibiting cannabinoid receptor binding activity (Ki = 0.47 [mu]M). A secondary research objective has been the structure-activity relationship (SAR) study to investigate the active pharmacophore in the lyngbyamide family of compounds, which consist of a cyclopropyl fatty acid (tail) and an amide head group. In total, 50 analogs were synythesized, designed to probe the importance of several structural characteristics of the lyngbyamides. These compounds were tested in a wide array of biological assays, and a subset were found to possess strong activity in the stabilization of cathepsin L-mediated proteolysis, brine shrimp toxicity, and surface tension suppression

Published
2014

22. Semisynthetic blasticidin S ester derivatives show enhanced antibiotic activityElectronic supplementary information (ESI) available. See DOI: https://doi.org/10.1039/d2md00412g

Author

Gannett, Cole, Banks, Paige, Chuong, Christina, Weger-Lucarelli, James, Mevers, Emily, and Lowell, Andrew N.

Abstract

A rich potential source of new antibiotics are undeveloped natural product cytotoxins, provided they can be derivatized to restrict their activity to bacteria. In this work, we describe modification of one such candidate, the broad-spectrum, translation termination inhibitor, blasticidin S. By semisynthetically modifying blasticidin S, we produced a series of ester derivatives of this highly polar, zwitterionic compound in a single step. These derivatives showed a marked increase in activity against Gram-positive bacteria and an increase in selectivity index for pathogenic bacteria over human cells. The results of this study suggest that semisynthetic derivatization of blasticidin S and other neglected natural product antimicrobials has the potential to increase their activity against and selectivity for bacteria, an approach that can be leveraged for the development of leads against antimicrobial resistant pathogens.

Published
2023
Full Text
View/download PDF

24. Chemical Exchanges between Multilateral Symbionts

Author

Bae, Munhyung, primary, Mevers, Emily, additional, Pishchany, Gleb, additional, Whaley, Sarah G., additional, Rock, Charles O., additional, Andes, David R., additional, Currie, Cameron R., additional, Pupo, Monica T., additional, and Clardy, Jon, additional

Published
2021
Full Text
View/download PDF

31. Deoxybuzonamine Isomers from the Millipede Brachycybe lecontii(Platydesmida: Andrognathidae)

Author

Jones, Tappey H., Harrison, Daniel P., Menegatti, Carla, Mevers, Emily, Knott, Kenneth, Marek, Paul, Hennen, Derek A., Kasson, Matt T., Macias, Angie M., Lovett, Brian, and Saporito, Ralph A.

Abstract

Millipedes (Diplopoda) are well known for their toxic or repellent defensive secretions. Here, we describe (6aR,10aS,10bR)-8,8-dimethyldodecahydropyrrolo[2,1-a]isoquinoline [trans-anti-trans-deoxybuzonamine (1a)] and (rel-6aR,10aR,10bR)-8,8-dimethyldodecahydropyrrolo[2,1-a]isoquinoline [trans-syn-cis-deoxybuzonamine (1b)], two isomers of deoxybuzonamine found in the chemical defense secretions of the millipede Brachycybe lecontiiWood (Colobognatha, Platydesmida, Andrognathidae). The carbon–nitrogen skeleton of these compounds was determined from their MS and GC-FTIR spectra obtained from the MeOH extract of whole millipedes, along with a subsequent selective synthesis. Their structures were established from their 1D (1H, 13C) and 2D NMR (COSY, NOESY, multiplicity-edited HSQC, HSQC-TOCSY, HMBC) spectra. Additionally, computational chemistry (DFT and DP4) was used to identify the relative configurations of 1aand 1bby comparing predicted 13C data to their experimental values, and the absolute configuration of 1awas determined by comparing its experimental specific rotation with that of the computationally calculated value. This is the first report of dodecahydropyrrolo[2,1-a]isoquinoline alkaloids from a platydesmidan millipede.

Published
2022
Full Text
View/download PDF

36. Canvass: A Crowd-Sourced, Natural Product Screening Library for Exploring Biological Space

Author

Kearney, Sara E., primary, Zahoránszky-Kőhalmi, Gergely, primary, Brimacombe, Kyle R., primary, Henderson, Mark J., primary, Lynch, Caitlin, primary, Zhao, Tongan, primary, Wan, Kanny K., primary, Itkin, Zina, primary, Dillon, Christopher, primary, Shen, Min, primary, Cheff, Dorian M., primary, Lee, Tobie D., primary, Bougie, Danielle, primary, Cheng, Ken, primary, Coussens, Nathan, primary, Dorjsuren, Dorjbal, primary, Eastman, Richard T., primary, Huang, Ruili, primary, Iannotti, Mike, primary, Karavadhi, Surendra, primary, Klumpp-Thomas, Carleen, primary, Roth, Jacob, primary, Sakamuru, Srilatha, primary, Sun, Wei, primary, Titus, Steven A., primary, Yasgar, Adam, primary, Zhang, Ya-Qin, primary, Zhao, Jinghua, primary, Andrade, Rodrigo B., primary, Brown, M. Kevin, primary, Burns, Noah Z., primary, Cha, Jin K., primary, Mevers, Emily E., primary, Clardy, Jon, primary, Clement, Jason A., primary, Crooks, Peter A., primary, Cuny, Gregory D., primary, Ganor, Jake, primary, Moreno, Jesus, primary, Morrill, LucasA., primary, Picazo, Elias, primary, Susick, Robert B., primary, Garg, Neil K., primary, Goess, Brian C., primary, B. Grossman, Robert, primary, Hughes, ChambersC., primary, Johnston, Jeffrey N., primary, Joullié, Madeleine M., primary, Kinghorn, A. Douglas, primary, Kingston, David G.I., primary, Krische, Michael J., primary, Kwon, Ohyun, primary, Maimone, Thomas J., primary, Majumdar, Susruta, primary, Maloney, Katherine N., primary, Mohamed, Enas, primary, Murphy, Brian T., primary, Nagorny, Pavel, primary, Olson, David E., primary, Overman, Larry E., primary, Brown, Lauren E., primary, Snyder, John K., primary, A. Porco, Jr., John, primary, Rivas, Fatima, primary, Ross, Samir A., primary, Sarpong, Richmond, primary, Sharma, Indrajeet, primary, Shaw, Jared T., primary, Xu, Zhengren, primary, Shen, Ben, primary, Shi, Wei, primary, Stephenson, Corey, primary, Verano, Alyssa L., primary, Tan, Derek S., primary, Tang, Yi, primary, Taylor, Richard E., primary, Thomson, Regan J., primary, Vosburg, David A., primary, Wu, Jimmy, primary, Wuest, William M., primary, Zakarian, Armen, primary, Zhang, Yufeng, primary, Ren, Tianjing, primary, Zuo, Zhong, primary, Inglese, James, primary, Michael, Sam, primary, Simeonov, Anton, primary, Zheng, Wei, primary, Shinn, Paul, primary, Jadhav, Ajit, primary, Boxer, Matthew B., primary, Hall, Matthew D., primary, Xia, Menghang, primary, Guha, Rajarshi, primary, and Rohde, Jason M., primary

Published
2018
Full Text
View/download PDF

40. Oridonin inhibits aberrant AKT activation in breast cancer

Author

Sun, Bowen, primary, Wang, Geng, additional, Liu, Huidong, additional, Liu, Pian, additional, Twal, Waleed O., additional, Cheung, Hiuwing, additional, Carroll, Steven L., additional, Ethier, Stephen P., additional, Mevers, Emily E., additional, Clardy, Jon, additional, Roberts, Thomas, additional, Chen, Changbin, additional, Li, Qian, additional, Wang, Lanfeng, additional, Yang, Meixiang, additional, Zhao, Jean J., additional, and Wang, Qi, additional

Published
2018
Full Text
View/download PDF

42. Homodimericin A: A Complex Hexacyclic Fungal Metabolite

Author

Mevers, Emily, primary, Saurí, Josep, additional, Liu, Yizhou, additional, Moser, Arvin, additional, Ramadhar, Timothy R., additional, Varlan, Maria, additional, Williamson, R. Thomas, additional, Martin, Gary E., additional, and Clardy, Jon, additional

Published
2016
Full Text
View/download PDF

50. Parguerene and Precarriebowmide, Two Classes of Lipopeptides from the Marine Cyanobacterium Moorea producens

Author

Mevers, Emily, Byrum, Tara, and Gerwick, William H.

Abstract

Two new marine cyanobacterial natural products, parguerene (1) and precarriebowmide (2), were isolated from a collection of Moorea producensobtained from La Parguera, Puerto Rico. The planar structures of both were deduced by 2D NMR spectroscopy and mass spectrometry. Parguerene is a modified acyl amide with some structural similarity to the bacterial metabolite stipiamide (3), whereas precarriebowmide is a lipopeptide and represents a minor modification compared to two other known metabolites, carriebowmide (4) and carriebowmide sulfone (5). The identification of 2led to an investigation into whether carriebowmide and carriebowmide sulfone were true secondary metabolites or isolation artifacts.

Published
2013
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results