Abstract：
:Here we present a natural product discovery approach, whereby structures are bioinformatically predicted from primary sequence and produced by chemical synthesis (synthetic-bioinformatic natural products, syn-BNPs), circumventing the need for bacterial culture and gene expression. When we applied the approach to nonribosomal peptide synthetase gene clusters from human-associated bacteria, we identified the humimycins. These antibiotics inhibit lipid II flippase and potentiate β-lactam activity against methicillin-resistant Staphylococcus aureus in mice, potentially providing a new treatment regimen.
journal_name
Nat Chem Bioljournal_title
Nature chemical biologyauthors
Chu J,Vila-Farres X,Inoyama D,Ternei M,Cohen LJ,Gordon EA,Reddy BV,Charlop-Powers Z,Zebroski HA,Gallardo-Macias R,Jaskowski M,Satish S,Park S,Perlin DS,Freundlich JS,Brady SFdoi
10.1038/nchembio.2207subject
Has Abstractpub_date
2016-12-01 00:00:00pages
1004-1006issue
12eissn
1552-4450issn
1552-4469pii
nchembio.2207journal_volume
12pub_type
杂志文章abstract：:Despite the fundamental roles of sialyl- and fucosyltransferases in mammalian physiology, there are few pharmacological tools to manipulate their function in a cellular setting. Although fluorinated analogs of the donor substrates are well-established transition state inhibitors of these enzymes, they are not membrane...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.999
更新日期：2012-07-01 00:00:00
abstract：:We describe a new technology for recruiting specific proteins to RNA through selective recognition of heteroduplexes formed with chemically modified antisense oligonucleotides (ASOs). Typically, ASOs function by hybridizing to their RNA targets and blocking the binding of single-stranded RNA-binding proteins. Unexpect...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.939
更新日期：2012-04-15 00:00:00
abstract：:Clinically significant antibiotic resistance has evolved against virtually every antibiotic deployed. Yet the development of new classes of antibiotics has lagged far behind our growing need for such drugs. Rather than focusing on therapeutics that target in vitro viability, much like conventional antibiotics, an alte...
journal_title：Nature chemical biology
pub_type： 杂志文章,评审
doi：10.1038/nchembio.2007.24
更新日期：2007-09-01 00:00:00
abstract：:We report here that fat mass and obesity-associated protein (FTO) has efficient oxidative demethylation activity targeting the abundant N6-methyladenosine (m(6)A) residues in RNA in vitro. FTO knockdown with siRNA led to increased amounts of m(6)A in mRNA, whereas overexpression of FTO resulted in decreased amounts of...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.687
更新日期：2011-10-16 00:00:00
abstract：:Mucopolysaccharidosis type I (MPS I), caused by mutations in the gene encoding α-L-iduronidase (IDUA), is one of approximately 70 genetic disorders collectively known as the lysosomal storage diseases. To gain insight into the basis for MPS I, we crystallized human IDUA produced in an Arabidopsis thaliana cgl mutant. ...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.1357
更新日期：2013-11-01 00:00:00
abstract：:Binding to the primary receptor, CD4, triggers conformational changes in the metastable HIV-1 envelope glycoprotein (Env) trimer ((gp120-gp41)3) that are important for virus entry into host cells. These changes include an 'opening' of the trimer, creation of a binding site for the CCR5 co-receptor and formation and/or...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.1623
更新日期：2014-10-01 00:00:00
abstract：:Protein kinase signaling along the kinetochore-centromere axis is crucial to assure mitotic fidelity, yet the details of its spatial coordination are obscure. Here, we examined how pools of human Polo-like kinase 1 (Plk1) within this axis control signaling events to elicit mitotic functions. To do this, we restricted ...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.2060
更新日期：2016-06-01 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：:We engineered a photoactivatable system for rapidly and reversibly exporting proteins from the nucleus by embedding a nuclear export signal in the LOV2 domain from phototropin 1. Fusing the chromatin modifier Bre1 to the photoswitch, we achieved light-dependent control of histone H2B monoubiquitylation in yeast, revea...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.2068
更新日期：2016-06-01 00:00:00
abstract：:Here we identify the amino acid transporter AnsP1 as the unique aspartate importer in the human pathogen Mycobacterium tuberculosis. Metabolomic analysis of a mutant with an inactive AnsP1 revealed that the transporter is essential for M. tuberculosis to assimilate nitrogen from aspartate. Virulence of the AnsP1 mutan...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.1355
更新日期：2013-11-01 00:00:00
abstract：:Only 25% of bacterial membrane transporters have functional annotation owing to the difficulty of experimental study and of accurate prediction of their function. Here we report a sequence-independent method for high-throughput mining of novel transporters. The method is based on ligand-responsive biosensor systems th...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.2189
更新日期：2016-12-01 00:00:00
abstract：:Pseudouridine synthases (PUSs) are responsible for installation of pseudouridine (Ψ) modification in RNA. However, the activity and function of the PUS enzymes remain largely unexplored. Here we focus on human PUS10 and find that it co-expresses with the microprocessor (DROSHA-DGCR8 complex). Depletion of PUS10 result...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/s41589-019-0420-5
更新日期：2020-02-01 00:00:00
abstract：:The sea lamprey is an ancient, parasitic fish that invaded the Great Lakes a century ago, where it triggered the collapse of many fisheries. Like many fishes, this species relies on chemical cues to mediate key aspects of its life, including migration and reproduction. Here we report the discovery of a multicomponent ...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio739
更新日期：2005-11-01 00:00:00
abstract：:What do organic synthesis, mechanistic enzymology, structural biology and glycoscience have in common? They all span chemistry and biology, benefit from and contribute to multidisciplinary approaches, and were up for discussion at a recent symposium in Dublin. ...
journal_title：Nature chemical biology
pub_type：
doi：10.1038/nchembio0206-59
更新日期：2006-02-01 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：:The eukaryotic 26S proteasome controls cellular processes by degrading specific regulatory proteins. Most proteins are targeted for degradation by a signal or degron that consists of two parts: a proteasome-binding tag, typically covalently attached polyubiquitin chains, and an unstructured region that serves as the i...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.521
更新日期：2011-03-01 00:00:00
abstract：:F(1)-ATPase is an ATP-driven rotary motor protein in which the γ-subunit rotates against the catalytic stator ring. Although the reaction scheme of F(1) has mostly been revealed, the timing of inorganic phosphate (P(i)) release remains controversial. Here we addressed this issue by verifying the reversibility of ATP h...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.443
更新日期：2010-11-01 00:00:00
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 c...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.2537
更新日期：2018-02-01 00:00:00
abstract：:We describe Scaffold Hunter, a highly interactive computer-based tool for navigation in chemical space that fosters intuitive recognition of complex structural relationships associated with bioactivity. The program reads compound structures and bioactivity data, generates compound scaffolds, correlates them in a hiera...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.187
更新日期：2009-08-01 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：:Long noncoding RNAs (lncRNAs) are important for gene expression, but little is known about their structures. RepA is a 1.6-kb mouse lncRNA comprising the same sequence as the 5' region of Xist, including A and F repeats. It has been proposed to facilitate the initiation and spread of X-chromosome inactivation, althoug...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.2272
更新日期：2017-03-01 00:00:00
abstract：:Although the protein synthesis inhibitor cycloheximide (CHX) has been known for decades, its precise mechanism of action remains incompletely understood. The glutarimide portion of CHX is seen in a family of structurally related natural products including migrastatin, isomigrastatin and lactimidomycin (LTM). We found ...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.304
更新日期：2010-03-01 00:00:00
abstract：:Single-molecule observations reveal that lipid- and protein-based interactions jointly contribute to the interactions among glycosylphosphatidylinositol-anchored proteins in membranes. Understanding these interactions will help to refine long-evolving (and still debated) models of 'raft' domains in biological membrane...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.1045
更新日期：2012-09-01 00:00:00
abstract：:Antibody-drug conjugates (ADCs) selectively deliver chemotherapeutic agents to target cells and are important cancer therapeutics. However, the mechanisms by which ADCs are internalized and activated remain unclear. Using CRISPR-Cas9 screens, we uncover many known and novel endolysosomal regulators as modulators of AD...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/s41589-019-0342-2
更新日期：2019-10-01 00:00:00
abstract：:Serine is both a proteinogenic amino acid and the source of one-carbon units essential for de novo purine and deoxythymidine synthesis. In the canonical pathway of glucose-derived serine synthesis, Homo sapiens phosphoglycerate dehydrogenase (PHGDH) catalyzes the first, rate-limiting step. Genetic loss of PHGDH is tox...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.2070
更新日期：2016-06-01 00:00:00
abstract：:Kinetochores act as hubs for multiple activities during cell division, including microtubule interactions and spindle checkpoint signaling. Each kinetochore can act autonomously, and activities change rapidly as proteins are recruited to, or removed from, kinetochores. Understanding this dynamic system requires tools ...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.2456
更新日期：2017-10-01 00:00:00
abstract：:Naturally produced polybrominated diphenyl ethers (PBDEs) pervade the marine environment and structurally resemble toxic man-made brominated flame retardants. PBDEs bioaccumulate in marine animals and are likely transferred to the human food chain. However, the biogenic basis for PBDE production in one of their most p...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.2330
更新日期：2017-05-01 00:00:00
abstract：:Polyglutamine (polyQ) stretches exceeding a threshold length confer a toxic function to proteins that contain them and cause at least nine neurological disorders. The basis for this toxicity threshold is unclear. Although polyQ expansions render proteins prone to aggregate into inclusion bodies, this may be a neuronal...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.694
更新日期：2011-10-30 00:00:00
abstract：:Transcription factors have diverse roles during embryonic development, combinatorially controlling cellular states in a spatially and temporally defined manner. Resolving the dynamic transcriptional profiles that underlie these patterning processes is essential for understanding embryogenesis at the molecular level. H...
journal_title：Nature chemical biology
pub_type： 杂志文章
doi：10.1038/nchembio.772
更新日期：2012-01-29 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
