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, we introduce an effective 6BrIG production strategy in Escherichia coli using tryptophan 6-halogenase SttH, tryptophanase TnaA and flavin-containing monooxygenase MaFMO. Since tryptophan halogenases are expressed in highly insoluble forms in E. coli, a flavin reductase (Fre) that regenerates FADH2 for the halogenase reaction was used as an N-terminal soluble tag of SttH. A consecutive two-cell reaction system was designed to overproduce regiospecifically brominated precursors of 6BrIG by spatiotemporal separation of bromination and bromotryptophan degradation. These approaches led to 315.0 mg l-1 6BrIG production from tryptophan and successful synthesis of regiospecifically dihalogenated indigos. Furthermore, it was demonstrated that 6BrIG overproducing cells can be directly used as a bacterial dye.
journal_name
Nat Chem Bioljournal_title
Nature chemical biologyauthors
Lee J,Kim J,Song JE,Song WS,Kim EJ,Kim YG,Jeong HJ,Kim HR,Choi KY,Kim BGdoi
10.1038/s41589-020-00684-4subject
Has Abstractpub_date
2021-01-01 00:00:00pages
104-112issue
1eissn
1552-4450issn
1552-4469pii
10.1038/s41589-020-00684-4journal_volume
17pub_type
杂志文章abstract::Lysine riboswitches are bacterial RNA structures that sense the concentration of lysine and regulate the expression of lysine biosynthesis and transport genes. Members of this riboswitch class are found in the 5' untranslated region of messenger RNAs, where they form highly selective receptors for lysine. Lysine bindi...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio842
更新日期:2007-01-01 00:00:00
abstract::The molecular forces that drive structural transitions between the open and closed states of channels and transporters are not well understood. The gate of the OmpA channel is formed by the central Glu52-Arg138 salt bridge, which can open to form alternate ion pairs with Lys82 and Glu128. To gain deeper insight into t...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio827
更新日期:2006-11-01 00:00:00
abstract::Enzymatic incorporation of a halogen atom is a common feature in the biosyntheses of more than 4,500 natural products. Halogenation of unactivated carbon centers in the biosyntheses of several compounds of nonribosomal peptide origin is carried out by a class of mononuclear nonheme iron enzymes that require alpha-keto...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio856
更新日期:2007-02-01 00:00:00
abstract::Foldamers are sequence-specific oligomers akin to peptides, proteins and oligonucleotides that fold into well-defined three-dimensional structures. They offer the chemical biologist a broad pallet of building blocks for the construction of molecules that test and extend our understanding of protein folding and functio...
journal_title:Nature chemical biology
pub_type: 杂志文章,评审
doi:10.1038/nchembio876
更新日期:2007-05-01 00:00:00
abstract::Signal transduction, regulatory processes and pharmaceutical responses are highly dependent upon ligand residence times. Gaining insight into how physical factors influence residence times (1/k(off)) should enhance our ability to manipulate biological interactions. We report experiments that yield structural insight i...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.769
更新日期:2012-01-15 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::Serine hydrolases play diverse roles in regulating host-pathogen interactions in a number of organisms, yet few have been characterized in the human pathogen Staphylococcus aureus. Here we describe a chemical proteomic screen that identified ten previously uncharacterized S. aureus serine hydrolases that mostly lack h...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-018-0060-1
更新日期:2018-06-01 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::Intracellular Ca(2+) regulates numerous proteins and cellular functions and can vary substantially over submicron and submillisecond scales, so precisely localized fast detection is desirable. We have created a approximately 1-kDa biarsenical Ca(2+) indicator, called Calcium Green FlAsH (CaGF, 1), to probe [Ca(2+)] su...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2007.4
更新日期:2007-07-01 00:00:00
abstract::The GATOR1 (SEACIT) complex consisting of Iml1-Npr2-Npr3 inhibits target of rapamycin complex 1 (TORC1) in response to amino acid insufficiency. In glucose medium, Saccharomyces cerevisiae mutants lacking the function of this complex grow poorly in the absence of amino acid supplementation, despite showing hallmarks o...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2478
更新日期:2017-11-01 00:00:00
abstract::Small ubiquitin-like modifier (SUMO) family proteins regulate target-protein functions by post-translational modification. However, a potent and selective inhibitor targeting the SUMO pathway has been lacking. Here we describe ML-792, a mechanism-based SUMO-activating enzyme (SAE) inhibitor with nanomolar potency in c...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2463
更新日期:2017-11-01 00:00:00
abstract::Targeted protein degradation via small-molecule modulation of cereblon offers vast potential for the development of new therapeutics. Cereblon-binding therapeutics carry the safety risks of thalidomide, which caused an epidemic of severe birth defects characterized by forelimb shortening or phocomelia. Here we show th...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-018-0129-x
更新日期:2018-10-01 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::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::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::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::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::Controlled distribution of lipids across various cell membranes is crucial for cell homeostasis and regulation. We developed an imaging method that allows simultaneous in situ quantification of cholesterol in two leaflets of the plasma membrane (PM) using tunable orthogonal cholesterol sensors. Our imaging revealed ma...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2268
更新日期:2017-03-01 00:00:00
abstract::Biosynthesis enables renewable production of manifold compounds, yet often biosynthetic performance must be improved for it to be economically feasible. Nongenetic, cell-to-cell variations in protein and metabolite concentrations are naturally inherent, suggesting the existence of both high- and low-performance varian...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2046
更新日期:2016-05-01 00:00:00
abstract::Bacterial biofilms can be programmed to produce living materials with self-healing and evolvable functionalities. However, the wider use of artificial biofilms has been hindered by limitations on processability and functional protein secretion capacity. We describe a highly flexible and tunable living functional mater...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-018-0169-2
更新日期:2019-01-01 00:00:00
abstract::Secondary structure refolding is a key event in biology as it modulates the conformation of many proteins in the cell, generating functional or aberrant states. The crystal structures of mannosyltransferase PimA reveal an exceptional flexibility of the protein along the catalytic cycle, including β-strand-to-α-helix a...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1694
更新日期:2015-01-01 00:00:00
abstract::Conditional cooperativity is a common mechanism involved in transcriptional regulation of prokaryotic type II toxin-antitoxin operons and is intricately related to bacterial persistence. It allows the toxin component of a toxin-antitoxin module to act as a co-repressor at low doses of toxin as compared to antitoxin. W...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2078
更新日期:2016-07-01 00:00:00
abstract::Naphthalene (1) and para-dichlorobenzene (PDCB, 2), which are widely used as moth repellents and air fresheners, cause cancer in rodents and are potential human carcinogens. However, their mechanisms of action remain unclear. Here we describe a novel method for delivering and screening hydrophobic chemicals in C. eleg...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio791
更新日期:2006-06-01 00:00:00
abstract::Glycosyltransferases are ubiquitous enzymes that catalyze the assembly of glycoconjugates throughout all kingdoms of nature. A long-standing problem is the rational design of probes that can be used to manipulate glycosyltransferase activity in cells and tissues. Here we describe the rational design and synthesis of a...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.520
更新日期:2011-03-01 00:00:00
abstract::Bioinorganic chemistry remains a vibrant discipline at the interface of chemistry and the biological sciences. Metal ions function in numerous metalloenzymes, are incorporated into pharmaceuticals and imaging agents, and inspire the synthesis of catalysts used to achieve many chemical transformations. ...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio1006-504
更新日期:2006-10-01 00:00:00
abstract::Thioredoxin (Trx) is one of the two major thiol antioxidants, playing essential roles in redox homeostasis and signaling. Despite its importance, there is a lack of methods for monitoring Trx redox dynamics in live cells, hindering a better understanding of physiological and pathological roles of the Trx redox system....
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2417
更新日期:2017-09-01 00:00:00
abstract::N-Acetylglucosamine β-O-linked to nucleocytoplasmic proteins (O-GlcNAc) is implicated in the regulation of gene expression in organisms, from humans to Drosophila melanogaster. Within Drosophila, O-GlcNAc transferase (OGT) is one of the Polycomb group proteins (PcGs) that act through Polycomb group response elements (...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2247
更新日期:2017-02-01 00:00:00
abstract::The resistance of Caenorhabditis elegans to pharmacological perturbation limits its use as a screening tool for novel small bioactive molecules. One strategy to improve the hit rate of small-molecule screens is to preselect molecules that have an increased likelihood of reaching their target in the worm. To learn whic...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.380
更新日期:2010-07-01 00:00:00
abstract::The heat shock protein 90 (Hsp90) has a critical role in malignant transformation. Whereas its ability to maintain the functional conformations of mutant and aberrant oncoproteins is established, a transformation-specific regulation of the antiapoptotic phenotype by Hsp90 is poorly understood. By using selective compo...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2007.10
更新日期:2007-08-01 00:00:00
abstract::More than 30 years ago, a calcium-dependent enzyme activity was described that generates N-acyl phosphatidylethanolamines (NAPEs), which are precursors for N-acyl ethanolamine (NAE) lipid transmitters, including the endocannabinoid anandamide. The identity of this calcium-dependent N-acyltransferase (Ca-NAT) has remai...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2127
更新日期:2016-09-01 00:00:00