Abstract：
:Chemistry drives many biological interactions between the microbiota and host animals, yet it is often challenging to identify the chemicals involved. This poses a problem, as such small molecules are excellent sources of potential pharmaceuticals, pretested by nature for animal compatibility. We discovered anti-HIV compounds from small, marine tunicates from the Eastern Fields of Papua New Guinea. Tunicates are a reservoir for new bioactive chemicals, yet their small size often impedes identification or even detection of the chemicals within. We solved this problem by combining chemistry, metagenomics, and synthetic biology to directly identify and synthesize the natural products. We show that these anti-HIV compounds, the divamides, are a novel family of lanthipeptides produced by symbiotic bacteria living in the tunicate. Neighboring animal colonies contain structurally related divamides that differ starkly in their biological properties, suggesting a role for biosynthetic plasticity in a native context wherein biological interactions take place.
journal_name
Nat Chem Bioljournal_title
Nature chemical biologyauthors
Smith TE,Pond CD,Pierce E,Harmer ZP,Kwan J,Zachariah MM,Harper MK,Wyche TP,Matainaho TK,Bugni TS,Barrows LR,Ireland CM,Schmidt EWdoi
10.1038/nchembio.2537subject
Has Abstractpub_date
2018-02-01 00:00:00pages
179-185issue
2eissn
1552-4450issn
1552-4469pii
nchembio.2537journal_volume
14pub_type
杂志文章abstract：:Phenylketonuria (PKU) is characterized by phenylalanine accumulation and progressive mental retardation caused by an unknown mechanism. We demonstrate that at pathological concentrations, phenylalanine self-assembles into fibrils with amyloid-like morphology and well-ordered electron diffraction. These assemblies are ...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.1002
更新日期：2012-08-01 00:00:00
abstract：:DNA polymerases catalyze efficient and high-fidelity DNA synthesis. While this reaction favors nucleotide incorporation, polymerases also catalyze a reverse reaction, pyrophosphorolysis, that removes the DNA primer terminus and generates deoxynucleoside triphosphates. Because pyrophosphorolysis can influence polymeras...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.2450
更新日期：2017-10-01 00:00:00
abstract：:The simultaneous observation of interdependent reactions within different phases as catalyzed by membrane-bound enzymes is still a challenging task. One such enzyme, the Escherichia coli integral membrane protein diacylglycerol kinase (DGK), is a key player in lipid regulation. It catalyzes the generation of phosphati...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.543
更新日期：2011-05-01 00:00:00
abstract：:Proteoglycans are complex glycoconjugates that regulate critical biological pathways in all higher organisms. Bikunin, the simplest proteoglycan, with a single glycosaminoglycan chain, is a serine protease inhibitor used to treat acute pancreatitis. Unlike nucleic acids and proteins, whose synthesis is template driven...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.673
更新日期：2011-10-09 00:00:00
abstract：: ...
journal_title：Nature chemical biology
pub_type： 评论,杂志文章
doi：10.1038/s41589-018-0073-9
更新日期：2018-06-01 00:00:00
abstract：:Protein serine-threonine kinase casein kinase II (CK2) is involved in a myriad of cellular processes including cell growth and proliferation through its phosphorylation of hundreds of substrates, yet how CK2 function is regulated is poorly understood. Here we report that the CK2 catalytic subunit CK2α is modified by O...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.771
更新日期：2012-01-22 00:00:00
abstract：:Thiolutin is a disulfide-containing antibiotic and anti-angiogenic compound produced by Streptomyces. Its biological targets are not known. We show that reduced thiolutin is a zinc chelator that inhibits the JAB1/MPN/Mov34 (JAMM) domain-containing metalloprotease Rpn11, a deubiquitinating enzyme of the 19S proteasome....
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.2370
更新日期：2017-07-01 00:00:00
abstract：: ...
journal_title：Nature chemical biology
pub_type： 评论,杂志文章
doi：10.1038/s41589-019-0230-9
更新日期：2019-03-01 00:00:00
abstract：:Mitochondrial electron transport drives ATP synthesis but also generates reactive oxygen species, which are both cellular signals and damaging oxidants. Superoxide production by respiratory complex III is implicated in diverse signaling events and pathologies, but its role remains controversial. Using high-throughput ...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.1910
更新日期：2015-11-01 00:00:00
abstract：:Genetic screens in cultured human cells represent a powerful unbiased strategy to identify cellular pathways that determine drug efficacy, providing critical information for clinical development. We used insertional mutagenesis-based screens in haploid cells to identify genes required for the sensitivity to lasonolide...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/s41589-019-0447-7
更新日期：2020-02-01 00:00:00
abstract：:Kinase inhibitors are important cancer drugs, but they tend to display limited target specificity, and their target profiles are often challenging to rationalize in terms of molecular mechanism. Here we report that the clinical kinase inhibitor bosutinib recognizes its kinase targets by engaging a pair of conserved st...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.1404
更新日期：2014-02-01 00:00:00
abstract：:Jasmonates are lipid-derived plant hormones that regulate plant defenses and numerous developmental processes. Although the biosynthesis and molecular function of the most active form of the hormone, (+)-7-iso-jasmonoyl-L-isoleucine (JA-Ile), have been unraveled, it remains poorly understood how the diversity of bioac...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.1591
更新日期：2014-10-01 00:00:00
abstract：:The inability of cells to properly fold, modify and assemble secretory and transmembrane proteins leads to accumulation of misfolded proteins in the endoplasmic reticulum (ER). Under these conditions of 'ER stress', cell survival depends on homeostatic benefits from an intracellular signaling pathway called the unfold...
journal_title：Nature chemical biology
pub_type： 杂志文章,评审
doi：10.1038/nchembio.1664
更新日期：2014-11-01 00:00:00
abstract：:Concatenation of engineered biocatalysts into multistep pathways markedly increases their utility, but the development of generalizable assembly methods remains a major challenge. Herein we evaluate 'bioretrosynthesis', which is an application of the retrograde evolution hypothesis, for biosynthetic pathway constructi...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.1494
更新日期：2014-05-01 00:00:00
abstract：:Targeted drugs are effective when they directly inhibit strong disease drivers, but only a small fraction of diseases feature defined actionable drivers. Alternatively, network-based approaches can uncover new therapeutic opportunities. Applying an integrated phenotypic screening, chemical and phosphoproteomics strate...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.2489
更新日期：2017-12-01 00:00:00
abstract：:Hundreds of human proteins are modified by reversible palmitoylation of cysteine residues (S-palmitoylation), but the regulation of depalmitoylation is poorly understood. Here, we develop 'depalmitoylation probes' (DPPs), small-molecule fluorophores, to monitor the endogenous activity levels of 'erasers' of S-palmitoy...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.2262
更新日期：2017-02-01 00:00:00
abstract：:RNA capping and decapping are thought to be distinctive features of eukaryotes. The redox cofactor NAD was recently discovered to be attached to small regulatory RNAs in bacteria in a cap-like manner, and Nudix hydrolase NudC was found to act as a NAD-decapping enzyme in vitro and in vivo. Here, crystal structures of ...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.2132
更新日期：2016-09-01 00:00:00
abstract：:Chemical biology is an interdisciplinary field that is undergoing rapid expansion around the globe. Recently, the Japanese Society for Chemical Biology sponsored its inaugural scientific meeting to discuss research at the interface of chemistry and biology. ...
journal_title：Nature chemical biology
pub_type：
doi：10.1038/nchembio0806-392
更新日期：2006-08-01 00:00:00
abstract：:Beyond established roles in collagen biosynthesis, hypoxic signaling and fatty acid metabolism, recent reports have now revealed roles for human 2-oxoglutarate-dependent oxygenases in histone and nucleic acid demethylation and in signaling protein hydroxylation. The emerging role of these oxygenases in enabling a mult...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio0308-152
更新日期：2008-03-01 00:00:00
abstract：:Twister is a small ribozyme present in almost all kingdoms of life that rapidly self-cleaves in variety of divalent metal ions. We used activity assays, bulk FRET and single-molecule FRET (smFRET) to understand how different metal ions promote folding and self-cleavage of the Oryza sativa twister ribozyme. Although mo...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.2459
更新日期：2017-10-01 00:00:00
abstract：:Cyclin-dependent kinase 9 (CDK9), an important regulator of transcriptional elongation, is a promising target for cancer therapy, particularly for cancers driven by transcriptional dysregulation. We characterized NVP-2, a selective ATP-competitive CDK9 inhibitor, and THAL-SNS-032, a selective CDK9 degrader consisting ...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.2538
更新日期：2018-02-01 00:00:00
abstract：:The ykkC family of bacterial riboswitches combines several widespread classes that have similar secondary structures and consensus motifs but control different genes in response to different cellular metabolites. Here we report the crystal structures of two distinct ykkC riboswitches specifically bound to their cognat...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/s41589-018-0114-4
更新日期：2018-09-01 00:00:00
abstract：:We report that simple glycoside donors can drastically shift the equilibria of glycosyltransferase-catalyzed reactions, transforming NDP-sugar formation from an endothermic to an exothermic process. To demonstrate the utility of this thermodynamic adaptability, we highlight the glycosyltransferase-catalyzed synthesis ...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.638
更新日期：2011-08-21 00:00:00
abstract：:Changes in cellular gene expression in response to small-molecule or genetic perturbations have yielded signatures that can connect unknown mechanisms of action (MoA) to ones previously established. We hypothesized that differential basal gene expression could be correlated with patterns of small-molecule sensitivity ...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.1986
更新日期：2016-02-01 00:00:00
abstract：:The actin cytoskeleton supports diverse cellular processes such as endocytosis, oriented growth, adhesion and migration. The dynamic nature of the cytoskeleton, however, has made it difficult to define the roles of the many accessory molecules that modulate actin organization, especially the multifunctional adapter pr...
journal_title：Nature chemical biology
pub_type： 信件
doi：10.1038/nchembio755
更新日期：2006-01-01 00:00:00
abstract：:Tyrian purple, mainly composed of 6,6'-dibromoindigo (6BrIG), is an ancient dye extracted from sea snails and was recently demonstrated as a biocompatible semiconductor material. However, its synthesis remains limited due to uncharacterized biosynthetic pathways and the difficulty of regiospecific bromination. Here, w...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/s41589-020-00684-4
更新日期：2021-01-01 00:00:00
abstract：:The catalytic activity of many protein kinases is controlled by conformational changes of a conserved Asp-Phe-Gly (DFG) motif. We used an infrared probe to track the DFG motif of the mitotic kinase Aurora A (AurA) and found that allosteric activation by the spindle-associated protein Tpx2 involves an equilibrium shift...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.2296
更新日期：2017-04-01 00:00:00
abstract：:The structure-specific nuclease human flap endonuclease-1 (hFEN1) plays a key role in DNA replication and repair and may be of interest as an oncology target. We present the crystal structure of inhibitor-bound hFEN1, which shows a cyclic N-hydroxyurea bound in the active site coordinated to two magnesium ions. Three ...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.2148
更新日期：2016-10-01 00:00:00
abstract：: ...
journal_title：Nature chemical biology
pub_type： 评论,杂志文章
doi：10.1038/s41589-018-0199-9
更新日期：2019-01-01 00:00:00
abstract：:Sulfoquinovose is produced by photosynthetic organisms at a rate of 10(10) tons per annum and is degraded by bacteria as a source of carbon and sulfur. We have identified Escherichia coli YihQ as the first dedicated sulfoquinovosidase and the gateway enzyme to sulfoglycolytic pathways. Structural and mutagenesis studi...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.2023
更新日期：2016-04-01 00:00:00
