In the version of the article originally published, the x axis of the graph in Fig. 4d was incorrectly labeled as "Retention time (min)". It should read "Reaction time (min)".
View Article and Find Full Text PDFThe soil microbiome can produce, resist, or degrade antibiotics and even catabolize them. While resistance genes are widely distributed in the soil, there is a dearth of knowledge concerning antibiotic catabolism. Here we describe a pathway for penicillin catabolism in four isolates.
View Article and Find Full Text PDFMost antibiotics are derived from the soil, but their catabolism there, which is necessary to close the antibiotic carbon cycle, remains uncharacterized. We report the first draft genome sequences of soil identified for subsisting solely on β-lactams as their carbon sources. The genomes encode multiple β-lactamases, although their antibiotic catabolic pathways remain enigmatic.
View Article and Find Full Text PDFThe microbial conversion of solid cellulosic biomass to liquid biofuels may provide a renewable energy source for transportation fuels. Endophytes represent a promising group of organisms, as they are a mostly untapped reservoir of metabolic diversity. They are often able to degrade cellulose, and they can produce an extraordinary diversity of metabolites.
View Article and Find Full Text PDFWe present genome engineering technologies that are capable of fundamentally reengineering genomes from the nucleotide to the megabase scale. We used multiplex automated genome engineering (MAGE) to site-specifically replace all 314 TAG stop codons with synonymous TAA codons in parallel across 32 Escherichia coli strains. This approach allowed us to measure individual recombination frequencies, confirm viability for each modification, and identify associated phenotypes.
View Article and Find Full Text PDFUnderstanding how individuals differ from one another and from closely related species is a fundamental problem in biology. Recent evidence suggests that much of the variation both within and between species is due to differential gene regulation. Here we review differential gene regulation focusing on evolutionary-developmental (evo-devo) biology, global comparison of genomic sequences, whole-genome gene expression, and transcription factor (TF) binding profiles.
View Article and Find Full Text PDFBiological data is often tabular but finding statistically valid connections between entities in a sequence of tables can be problematic--for example, connecting particular entities in a drug property table to gene properties in a second table, using a third table associating genes with drugs. Here we present an approach (CRIT) to find connections such as these and show how it can be applied in a variety of genomic contexts including chemogenomics data.
View Article and Find Full Text PDFA systems understanding of nuclear organization and events is critical for determining how cells divide, differentiate, and respond to stimuli and for identifying the causes of diseases. Chromatin remodeling complexes such as SWI/SNF have been implicated in a wide variety of cellular processes including gene expression, nuclear organization, centromere function, and chromosomal stability, and mutations in SWI/SNF components have been linked to several types of cancer. To better understand the biological processes in which chromatin remodeling proteins participate, we globally mapped binding regions for several components of the SWI/SNF complex throughout the human genome using ChIP-Seq.
View Article and Find Full Text PDFSummary: The advent of next-generation sequencing for functional genomics has given rise to quantities of sequence information that are often so large that they are difficult to handle. Moreover, sequence reads from a specific individual can contain sufficient information to potentially identify and genetically characterize that person, raising privacy concerns. In order to address these issues, we have developed the Mapped Read Format (MRF), a compact data summary format for both short and long read alignments that enables the anonymization of confidential sequence information, while allowing one to still carry out many functional genomics studies.
View Article and Find Full Text PDFNatural small compounds comprise most cellular molecules and bind proteins as substrates, products, cofactors, and ligands. However, a large-scale investigation of in vivo protein-small metabolite interactions has not been performed. We developed a mass spectrometry assay for the large-scale identification of in vivo protein-hydrophobic small metabolite interactions in yeast and analyzed compounds that bind ergosterol biosynthetic proteins and protein kinases.
View Article and Find Full Text PDFThe Patagonian fungal endophyte NRRL 50072 is reported to produce a variety of medium-chain and highly branched volatile organic compounds (VOCs) that have been highlighted for their potential as fuel alternatives and are collectively termed myco-diesel. To assess the novelty of this observation, we determined the extent to which ten closely related Ascocoryne strains from commercial culture collections possess similar VOC production capability. DNA sequencing established a high genetic similarity between NRRL 50072 and each Ascocoryne isolate, consistent with its reassignment as Ascocoryne sarcoides.
View Article and Find Full Text PDFRecent metagenomics studies have begun to sample the genomic diversity among disparate habitats and relate this variation to features of the environment. Membrane proteins are an intuitive, but thus far overlooked, choice in this type of analysis as they directly interact with the environment, receiving signals from the outside and transporting nutrients. Using global ocean sampling (GOS) data, we found nearly approximately 900,000 membrane proteins in large-scale metagenomic sequence, approximately a fifth of which are completely novel, suggesting a large space of hitherto unexplored protein diversity.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
February 2009
Recently, approaches have been developed to sample the genetic content of heterogeneous environments (metagenomics). However, by what means these sequences link distinct environmental conditions with specific biological processes is not well understood. Thus, a major challenge is how the usage of particular pathways and subnetworks reflects the adaptation of microbial communities across environments and habitats-i.
View Article and Find Full Text PDFCharacterization of interspecies differences in gene regulation is crucial for understanding the molecular basis of both phenotypic diversity and evolution. By means of chromatin immunoprecipitation and DNA microarray analysis, the divergence in the binding sites of the pseudohyphal regulators Ste12 and Tec1 was determined in the yeasts Saccharomyces cerevisiae, S. mikatae, and S.
View Article and Find Full Text PDFPathways are integral to systems biology. Their classical representation has proven useful but is inconsistent in the meaning assigned to each arrow (or edge) and inadvertently implies the isolation of one pathway from another. Conversely, modern high-throughput (HTP) experiments offer standardized networks that facilitate topological calculations.
View Article and Find Full Text PDFAcinetobacter baumannii has emerged as an important and problematic human pathogen as it is the causative agent of several types of infections including pneumonia, meningitis, septicemia, and urinary tract infections. We explored the pathogenic content of this harmful pathogen using a combination of DNA sequencing and insertional mutagenesis. The genome of this organism was sequenced using a strategy involving high-density pyrosequencing, a novel, rapid method of high-throughput sequencing.
View Article and Find Full Text PDFBackground: The ability to rapidly characterize an unknown microorganism is critical in both responding to infectious disease and biodefense. To do this, we need some way of anticipating an organism's phenotype based on the molecules encoded by its genome. However, the link between molecular composition (i.
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