204 research outputs found
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Antibiotic and Antimalarial Quinones from Fungus-Growing Ant-Associated Pseudonocardia sp.
Three new members of the angucycline class of antibiotics, pseudonocardones A–C (1–3), along with the known antibiotics 6-deoxy-8-O-methylrabelomycin (4) and X-14881 E (5) have been isolated from the culture of a Pseudonocardia strain associated with the fungus-growing ant Apterostigma dentigerum. Compounds 4 and 5 showed antibiotic activity against Bacillus subtilis 3610 and liver-stage Plasmodium berghei, while 1–3 were inactive or only weakly active in a variety of biological assays. Compound 5 also showed moderate cytotoxicity against HepG2 cells
Bactobolin Resistance Is Conferred by Mutations in the L2 Ribosomal Protein
Burkholderia thailandensis produces a family of polyketide-peptide molecules called bactobolins, some of which are potent antibiotics. We found that growth of B. thailandensis at 30°C versus that at 37°C resulted in increased production of bactobolins. We purified the three most abundant bactobolins and determined their activities against a battery of bacteria and mouse fibroblasts. Two of the three compounds showed strong activities against both bacteria and fibroblasts. The third analog was much less potent in both assays. These results suggested that the target of bactobolins might be conserved across bacteria and mammalian cells. To learn about the mechanism of bactobolin activity, we isolated four spontaneous bactobolin-resistant Bacillus subtilis mutants. We used genomic sequencing technology to show that each of the four resistant variants had mutations in rplB, which codes for the 50S ribosome-associated L2 protein. Ectopic expression of a mutant rplB gene in wild-type B. subtilis conferred bactobolin resistance. Finally, the L2 mutations did not confer resistance to other antibiotics known to interfere with ribosome function. Our data indicate that bactobolins target the L2 protein or a nearby site and that this is not the target of other antibiotics. We presume that the mammalian target of bactobolins involves the eukaryotic homolog of L2 (L8e)
Recommended from our members
Bactobolin Resistance Is Conferred by Mutations in the L2 Ribosomal Protein
Burkholderia thailandensis produces a family of polyketide-peptide molecules called bactobolins, some of which are potent antibiotics. We found that growth of B. thailandensis at 30°C versus that at 37°C resulted in increased production of bactobolins. We purified the three most abundant bactobolins and determined their activities against a battery of bacteria and mouse fibroblasts. Two of the three compounds showed strong activities against both bacteria and fibroblasts. The third analog was much less potent in both assays. These results suggested that the target of bactobolins might be conserved across bacteria and mammalian cells. To learn about the mechanism of bactobolin activity, we isolated four spontaneous bactobolin-resistant Bacillus subtilis mutants. We used genomic sequencing technology to show that each of the four resistant variants had mutations in rplB, which codes for the 50S ribosome-associated L2 protein. Ectopic expression of a mutant rplB gene in wild-type B. subtilis conferred bactobolin resistance. Finally, the L2 mutations did not confer resistance to other antibiotics known to interfere with ribosome function. Our data indicate that bactobolins target the L2 protein or a nearby site and that this is not the target of other antibiotics. We presume that the mammalian target of bactobolins involves the eukaryotic homolog of L2 (L8e)
AAK1 Identified as an Inhibitor of Neuregulin-1/ErbB4-Dependent Neurotrophic Factor Signaling Using Integrative Chemical Genomics and Proteomics
SummaryTarget identification remains challenging for the field of chemical biology. We describe an integrative chemical genomic and proteomic approach combining the use of differentially active analogs of small molecule probes with stable isotope labeling by amino acids in cell culture-mediated affinity enrichment, followed by subsequent testing of candidate targets using RNA interference-mediated gene silencing. We applied this approach to characterizing the natural product K252a and its ability to potentiate neuregulin-1 (Nrg1)/ErbB4 (v-erb-a erythroblastic leukemia viral oncogene homolog 4)-dependent neurotrophic factor signaling and neuritogenesis. We show that AAK1 (adaptor-associated kinase 1) is a relevant target of K252a, and that the loss of AAK1 alters ErbB4 trafficking and expression levels, providing evidence for a previously unrecognized role for AAK1 in Nrg1-mediated neurotrophic factor signaling. Similar strategies should lead to the discovery of novel targets for therapeutic development
The Multi-Object, Fiber-Fed Spectrographs for SDSS and the Baryon Oscillation Spectroscopic Survey
We present the design and performance of the multi-object fiber spectrographs
for the Sloan Digital Sky Survey (SDSS) and their upgrade for the Baryon
Oscillation Spectroscopic Survey (BOSS). Originally commissioned in Fall 1999
on the 2.5-m aperture Sloan Telescope at Apache Point Observatory, the
spectrographs produced more than 1.5 million spectra for the SDSS and SDSS-II
surveys, enabling a wide variety of Galactic and extra-galactic science
including the first observation of baryon acoustic oscillations in 2005. The
spectrographs were upgraded in 2009 and are currently in use for BOSS, the
flagship survey of the third-generation SDSS-III project. BOSS will measure
redshifts of 1.35 million massive galaxies to redshift 0.7 and Lyman-alpha
absorption of 160,000 high redshift quasars over 10,000 square degrees of sky,
making percent level measurements of the absolute cosmic distance scale of the
Universe and placing tight constraints on the equation of state of dark energy.
The twin multi-object fiber spectrographs utilize a simple optical layout
with reflective collimators, gratings, all-refractive cameras, and
state-of-the-art CCD detectors to produce hundreds of spectra simultaneously in
two channels over a bandpass covering the near ultraviolet to the near
infrared, with a resolving power R = \lambda/FWHM ~ 2000. Building on proven
heritage, the spectrographs were upgraded for BOSS with volume-phase
holographic gratings and modern CCD detectors, improving the peak throughput by
nearly a factor of two, extending the bandpass to cover 360 < \lambda < 1000
nm, and increasing the number of fibers from 640 to 1000 per exposure. In this
paper we describe the original SDSS spectrograph design and the upgrades
implemented for BOSS, and document the predicted and measured performances.Comment: 43 pages, 42 figures, revised according to referee report and
accepted by AJ. Provides background for the instrument responsible for SDSS
and BOSS spectra. 4th in a series of survey technical papers released in
Summer 2012, including arXiv:1207.7137 (DR9), arXiv:1207.7326 (Spectral
Classification), and arXiv:1208.0022 (BOSS Overview
Microtermolides A and B from Termite-Associated Streptomyces sp. and Structural Revision of Vinylamycin
Microtermolides A (1) and B (2) were isolated from a Streptomyces sp. strain associated with fungus-growing termites. The structures of 1 and 2 were determined by 1D- and 2D-NMR spectroscopy and high-resolution mass spectrometry. Structural elucidation of 1 led to the re-examination of the structure originally proposed for vinylamycin (3). Based on a comparison of predicted and experimental H and C NMR chemical shifts, we propose that vinylamycin’s structure be revised from 3 to 4
Sloan Digital Sky Survey Imaging of Low Galactic Latitude Fields: Technical Summary and Data Release
The Sloan Digital Sky Survey (SDSS) mosaic camera and telescope have obtained
five-band optical-wavelength imaging near the Galactic plane outside of the
nominal survey boundaries. These additional data were obtained during
commissioning and subsequent testing of the SDSS observing system, and they
provide unique wide-area imaging data in regions of high obscuration and star
formation, including numerous young stellar objects, Herbig-Haro objects and
young star clusters. Because these data are outside the Survey regions in the
Galactic caps, they are not part of the standard SDSS data releases. This paper
presents imaging data for 832 square degrees of sky (including repeats), in the
star-forming regions of Orion, Taurus, and Cygnus. About 470 square degrees are
now released to the public, with the remainder to follow at the time of SDSS
Data Release 4. The public data in Orion include the star-forming region NGC
2068/NGC 2071/HH24 and a large part of Barnard's loop.Comment: 31 pages, 9 figures (3 missing to save space), accepted by AJ, in
press, see http://photo.astro.princeton.edu/oriondatarelease for data and
paper with all figure
Mixing and matching siderophore clusters: structure and biosynthesis of serratiochelins from Serratia sp. v4
Studying the evolutionary history underlying the remarkable structures and biological activities of natural products has been complicated by not knowing the functions they have evolved to fulfill. Siderophores - soluble, low molecular weight compounds - have an easily understood and measured function: acquiring iron from the environment. Bacteria engage in a fierce competition for acquiring iron, which rewards the production of siderophores that bind iron tightly and cannot be used or pirated by competitors. The structures and biosyntheses of 'odd' siderophores can reveal the evolutionary strategy that led to their creation. Here, we here report a new Serratia strain that produces serratiochelin and an analog of serratiochelin. A genetic approach located the serratiochelin gene cluster, and targeted mutations in several genes implicated in serratiochelin biosynthesis were generated. Bioinformatic analyses and mutagenesis results demonstrate that genes from two well known siderophore clusters, the Escherichia coli enterobactin cluster and the Vibrio cholerae vibriobactin cluster, were shuffled to produce a new siderophore biosynthetic pathway. These results highlight how modular siderophore gene clusters can be mixed and matched during evolution to generate structural diversity in siderophores.This work was supported by the National Institutes of Health (Grants GM82137 to R.K., and AI057159 and GM086258 to J.C.). M.R.S. acknowledges support from the NIH Pathway to Independence Award (Grant 1K99 GM098299-01). S.C. and M.J.V. acknowledge support from the Portuguese Foundation for Science and Technology (PhD Grant SFRH/BD/38298/2007 to S.C.; Project PTDC/EBB-EBI/104263/2008 to M.J.V.)
The Fifth Data Release of the Sloan Digital Sky Survey
This paper describes the Fifth Data Release (DR5) of the Sloan Digital Sky
Survey (SDSS). DR5 includes all survey quality data taken through June 2005 and
represents the completion of the SDSS-I project (whose successor, SDSS-II will
continue through mid-2008). It includes five-band photometric data for 217
million objects selected over 8000 square degrees, and 1,048,960 spectra of
galaxies, quasars, and stars selected from 5713 square degrees of that imaging
data. These numbers represent a roughly 20% increment over those of the Fourth
Data Release; all the data from previous data releases are included in the
present release. In addition to "standard" SDSS observations, DR5 includes
repeat scans of the southern equatorial stripe, imaging scans across M31 and
the core of the Perseus cluster of galaxies, and the first spectroscopic data
from SEGUE, a survey to explore the kinematics and chemical evolution of the
Galaxy. The catalog database incorporates several new features, including
photometric redshifts of galaxies, tables of matched objects in overlap regions
of the imaging survey, and tools that allow precise computations of survey
geometry for statistical investigations.Comment: ApJ Supp, in press, October 2007. This paper describes DR5. The SDSS
Sixth Data Release (DR6) is now public, available from http://www.sdss.or
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