当前位置： SCI文献检索 > Nature Chemical Biology期刊下所有文献 > Using the pimeloyl-CoA synthetase adenylation fold to synthesize fatty acid thioesters.

Using the pimeloyl-CoA synthetase adenylation fold to synthesize fatty acid thioesters.

Abstract：

:Biotin is an essential vitamin in plants and mammals, functioning as the carbon dioxide carrier within central lipid metabolism. Bacterial pimeloyl-CoA synthetase (BioW) acts as a highly specific substrate-selection gate, ensuring the integrity of the carbon chain in biotin synthesis. BioW catalyzes the condensation of pimelic acid (C7 dicarboxylic acid) with CoASH in an ATP-dependent manner to form pimeloyl-CoA, the first dedicated biotin building block. Multiple structures of Bacillus subtilis BioW together capture all three substrates, as well as the intermediate pimeloyl-adenylate and product pyrophosphate (PPi), indicating that the enzyme uses an internal ruler to select the correct dicarboxylic acid substrate. Both the catalytic mechanism and the surprising stability of the adenylate intermediate were rationalized through site-directed mutagenesis. Building on this understanding, BioW was engineered to synthesize high-value heptanoyl (C7) and octanoyl (C8) monocarboxylic acid-CoA and C8 dicarboxylic-CoA products, highlighting the enzyme's synthetic potential.

journal_name

Nat Chem Biol

journal_title

Nature chemical biology

authors

Wang M,Moynié L,Harrison PJ,Kelly V,Piper A,Naismith JH,Campopiano DJ

doi

10.1038/nchembio.2361

subject

Has Abstract

pub_date

2017-06-01 00:00:00

pages

660-667

issue

6

eissn

1552-4450

issn

1552-4469

pii

nchembio.2361

journal_volume

13

pub_type

杂志文章

相关文献

Nature Chemical Biology文献大全
  • The role of distant mutations and allosteric regulation on LovD active site dynamics.

    abstract：:Natural enzymes have evolved to perform their cellular functions under complex selective pressures, which often require their catalytic activities to be regulated by other proteins. We contrasted a natural enzyme, LovD, which acts on a protein-bound (LovF) acyl substrate, with a laboratory-generated variant that was t...

    journal_title：Nature chemical biology

    pub_type： 杂志文章

    doi：10.1038/nchembio.1503

    authors： Jiménez-Osés G,Osuna S,Gao X,Sawaya MR,Gilson L,Collier SJ,Huisman GW,Yeates TO,Tang Y,Houk KN

    更新日期：2014-06-01 00:00:00

  • Targeting BAX to drug death directly.

    abstract：:BCL-2 family protein interactions regulate apoptosis, a critical process that maintains tissue homeostasis but can cause a host of human diseases when deregulated. Venetoclax is the first FDA-approved drug to reactivate apoptosis in cancer by selectively targeting an anti-apoptotic BCL-2 family member. The drug's acti...

    journal_title：Nature chemical biology

    pub_type： 杂志文章,评审

    doi：10.1038/s41589-019-0306-6

    authors： Walensky LD

    更新日期：2019-07-01 00:00:00

  • Small-molecule inhibition of siderophore biosynthesis in Mycobacterium tuberculosis and Yersinia pestis.

    abstract：:Mycobacterium tuberculosis and Yersinia pestis, the causative agents of tuberculosis and plague, respectively, are pathogens with serious ongoing impact on global public health and potential use as agents of bioterrorism. Both pathogens have iron acquisition systems based on siderophores, secreted iron-chelating compo...

    journal_title：Nature chemical biology

    pub_type： 杂志文章

    doi：10.1038/nchembio706

    authors： Ferreras JA,Ryu JS,Di Lello F,Tan DS,Quadri LE

    更新日期：2005-06-01 00:00:00

  • Mixture of new sulfated steroids functions as a migratory pheromone in the sea lamprey.

    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

    authors： Sorensen PW,Fine JM,Dvornikovs V,Jeffrey CS,Shao F,Wang J,Vrieze LA,Anderson KR,Hoye TR

    更新日期：2005-11-01 00:00:00

  • Pharmacological perturbation of CDK9 using selective CDK9 inhibition or degradation.

    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

    authors： Olson CM,Jiang B,Erb MA,Liang Y,Doctor ZM,Zhang Z,Zhang T,Kwiatkowski N,Boukhali M,Green JL,Haas W,Nomanbhoy T,Fischer ES,Young RA,Bradner JE,Winter GE,Gray NS

    更新日期：2018-02-01 00:00:00

  • Learning biological networks: from modules to dynamics.

    abstract：:Learning regulatory networks from genomics data is an important problem with applications spanning all of biology and biomedicine. Functional genomics projects offer a cost-effective means of greatly expanding the completeness of our regulatory models, and for some prokaryotic organisms they offer a means of learning ...

    journal_title：Nature chemical biology

    pub_type： 杂志文章,评审

    doi：10.1038/nchembio.122

    authors： Bonneau R

    更新日期：2008-11-01 00:00:00

  • Structure and function of the bacterial decapping enzyme NudC.

    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

    authors： Höfer K,Li S,Abele F,Frindert J,Schlotthauer J,Grawenhoff J,Du J,Patel DJ,Jäschke A

    更新日期：2016-09-01 00:00:00

  • Probing the roles of SUMOylation in cancer cell biology by using a selective SAE inhibitor.

    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

    authors： He X,Riceberg J,Soucy T,Koenig E,Minissale J,Gallery M,Bernard H,Yang X,Liao H,Rabino C,Shah P,Xega K,Yan ZH,Sintchak M,Bradley J,Xu H,Duffey M,England D,Mizutani H,Hu Z,Guo J,Chau R,Dick LR,Brownell JE,Ne

    更新日期：2017-11-01 00:00:00

  • Light-based control of metabolic flux through assembly of synthetic organelles.

    abstract：:To maximize a desired product, metabolic engineers typically express enzymes to high, constant levels. Yet, permanent pathway activation can have undesirable consequences including competition with essential pathways and accumulation of toxic intermediates. Faced with similar challenges, natural metabolic systems comp...

    journal_title：Nature chemical biology

    pub_type： 杂志文章

    doi：10.1038/s41589-019-0284-8

    authors： Zhao EM,Suek N,Wilson MZ,Dine E,Pannucci NL,Gitai Z,Avalos JL,Toettcher JE

    更新日期：2019-06-01 00:00:00

  • An enzyme-coupled biosensor enables (S)-reticuline production in yeast from glucose.

    abstract：:Benzylisoquinoline alkaloids (BIAs) are a diverse family of plant-specialized metabolites that include the pharmaceuticals codeine and morphine and their derivatives. Microbial synthesis of BIAs holds promise as an alternative to traditional crop-based manufacturing. Here we demonstrate the production of the key BIA i...

    journal_title：Nature chemical biology

    pub_type： 杂志文章

    doi：10.1038/nchembio.1816

    authors： DeLoache WC,Russ ZN,Narcross L,Gonzales AM,Martin VJ,Dueber JE

    更新日期：2015-07-01 00:00:00

  • Structural basis for hijacking siderophore receptors by antimicrobial lasso peptides.

    abstract：:The lasso peptide microcin J25 is known to hijack the siderophore receptor FhuA for initiating internalization. Here, we provide what is to our knowledge the first structural evidence on the recognition mechanism, and our biochemical data show that another closely related lasso peptide cannot interact with FhuA. Our w...

    journal_title：Nature chemical biology

    pub_type： 杂志文章

    doi：10.1038/nchembio.1499

    authors： Mathavan I,Zirah S,Mehmood S,Choudhury HG,Goulard C,Li Y,Robinson CV,Rebuffat S,Beis K

    更新日期：2014-05-01 00:00:00

  • Hijacking a biosynthetic pathway yields a glycosyltransferase inhibitor within cells.

    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

    authors： Gloster TM,Zandberg WF,Heinonen JE,Shen DL,Deng L,Vocadlo DJ

    更新日期：2011-03-01 00:00:00

  • Molecular basis for ubiquitin ligase CRL2FEM1C-mediated recognition of C-degron.

    abstract：:Proteome integrity depends on the ubiquitin-proteasome system to degrade unwanted or abnormal proteins. In addition to the N-degrons, C-terminal residues of proteins can also serve as degradation signals (C-degrons) that are recognized by specific cullin-RING ubiquitin ligases (CRLs) for proteasomal degradation. FEM1C...

    journal_title：Nature chemical biology

    pub_type： 杂志文章

    doi：10.1038/s41589-020-00703-4

    authors： Yan X,Wang X,Li Y,Zhou M,Li Y,Song L,Mi W,Min J,Dong C

    更新日期：2021-01-04 00:00:00

  • A reactivity-based probe of the intracellular labile ferrous iron pool.

    abstract：:Improved methods for studying intracellular reactive Fe(II) are of significant interest for studies of iron metabolism and disease-relevant changes in iron homeostasis. Here we describe a highly selective reactivity-based probe in which a Fenton-type reaction with intracellular labile Fe(II) leads to unmasking of the ...

    journal_title：Nature chemical biology

    pub_type： 杂志文章

    doi：10.1038/nchembio.2116

    authors： Spangler B,Morgan CW,Fontaine SD,Vander Wal MN,Chang CJ,Wells JA,Renslo AR

    更新日期：2016-09-01 00:00:00

  • Site-specific ubiquitination affects protein energetics and proteasomal degradation.

    abstract：:Changes in the cellular environment modulate protein energy landscapes to drive important biology, with consequences for signaling, allostery and other vital processes. The effects of ubiquitination are particularly important because of their potential influence on degradation by the 26S proteasome. Moreover, proteaso...

    journal_title：Nature chemical biology

    pub_type： 杂志文章

    doi：10.1038/s41589-020-0556-3

    authors： Carroll EC,Greene ER,Martin A,Marqusee S

    更新日期：2020-08-01 00:00:00

  • Inhibition of eukaryotic translation elongation by cycloheximide and lactimidomycin.

    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

    authors： Schneider-Poetsch T,Ju J,Eyler DE,Dang Y,Bhat S,Merrick WC,Green R,Shen B,Liu JO

    更新日期：2010-03-01 00:00:00

  • The radical SAM enzyme AlbA catalyzes thioether bond formation in subtilosin A.

    abstract：:Subtilosin A is a 35-residue, ribosomally synthesized bacteriocin encoded by the sbo-alb operon of Bacillus subtilis. It is composed of a head-to-tail circular peptide backbone that is additionally restrained by three unusual thioether bonds between three cysteines and the α-carbon of one threonine and two phenylalani...

    journal_title：Nature chemical biology

    pub_type： 杂志文章

    doi：10.1038/nchembio.798

    authors： Flühe L,Knappe TA,Gattner MJ,Schäfer A,Burghaus O,Linne U,Marahiel MA

    更新日期：2012-02-26 00:00:00

  • Analysis of modular bioengineered antimicrobial lanthipeptides at nanoliter scale.

    abstract：:The rise of antibiotic resistance demands the acceleration of molecular diversification strategies to inspire new chemical entities for antibiotic medicines. We report here on the large-scale engineering of ribosomally synthesized and post-translationally modified antimicrobial peptides carrying the ring-forming amino...

    journal_title：Nature chemical biology

    pub_type： 杂志文章

    doi：10.1038/s41589-019-0250-5

    authors： Schmitt S,Montalbán-López M,Peterhoff D,Deng J,Wagner R,Held M,Kuipers OP,Panke S

    更新日期：2019-05-01 00:00:00

  • Correlating chemical sensitivity and basal gene expression reveals mechanism of action.

    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

    authors： Rees MG,Seashore-Ludlow B,Cheah JH,Adams DJ,Price EV,Gill S,Javaid S,Coletti ME,Jones VL,Bodycombe NE,Soule CK,Alexander B,Li A,Montgomery P,Kotz JD,Hon CS,Munoz B,Liefeld T,Dančík V,Haber DA,Clish CB,Bittker JA

    更新日期：2016-02-01 00:00:00

  • Bioretrosynthetic construction of a didanosine biosynthetic pathway.

    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

    authors： Birmingham WR,Starbird CA,Panosian TD,Nannemann DP,Iverson TM,Bachmann BO

    更新日期：2014-05-01 00:00:00

  • Prolonged and tunable residence time using reversible covalent kinase inhibitors.

    abstract：:Drugs with prolonged on-target residence times often show superior efficacy, yet general strategies for optimizing drug-target residence time are lacking. Here we made progress toward this elusive goal by targeting a noncatalytic cysteine in Bruton's tyrosine kinase (BTK) with reversible covalent inhibitors. Using an ...

    journal_title：Nature chemical biology

    pub_type： 杂志文章

    doi：10.1038/nchembio.1817

    authors： Bradshaw JM,McFarland JM,Paavilainen VO,Bisconte A,Tam D,Phan VT,Romanov S,Finkle D,Shu J,Patel V,Ton T,Li X,Loughhead DG,Nunn PA,Karr DE,Gerritsen ME,Funk JO,Owens TD,Verner E,Brameld KA,Hill RJ,Goldstein DM,

    更新日期：2015-07-01 00:00:00

  • Evidence for dynamics in proteins as a mechanism for ligand dissociation.

    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

    authors： Carroll MJ,Mauldin RV,Gromova AV,Singleton SF,Collins EJ,Lee AL

    更新日期：2012-01-15 00:00:00

  • Chemical hijacking of auxin signaling with an engineered auxin-TIR1 pair.

    abstract：:The phytohormone auxin indole-3-acetic acid (IAA) regulates nearly all aspects of plant growth and development. Despite substantial progress in our understanding of auxin biology, delineating specific auxin response remains a major challenge. Auxin regulates transcriptional response via its receptors, TIR1 and AFB F-b...

    journal_title：Nature chemical biology

    pub_type： 杂志文章

    doi：10.1038/nchembio.2555

    authors： Uchida N,Takahashi K,Iwasaki R,Yamada R,Yoshimura M,Endo TA,Kimura S,Zhang H,Nomoto M,Tada Y,Kinoshita T,Itami K,Hagihara S,Torii KU

    更新日期：2018-03-01 00:00:00

  • 5-Formylcytosine can be a stable DNA modification in mammals.

    abstract：:5-Formylcytosine (5fC) is a rare base found in mammalian DNA and thought to be involved in active DNA demethylation. Here, we show that developmental dynamics of 5fC levels in mouse DNA differ from those of 5-hydroxymethylcytosine (5hmC), and using stable isotope labeling in vivo, we show that 5fC can be a stable DNA ...

    journal_title：Nature chemical biology

    pub_type： 杂志文章

    doi：10.1038/nchembio.1848

    authors： Bachman M,Uribe-Lewis S,Yang X,Burgess HE,Iurlaro M,Reik W,Murrell A,Balasubramanian S

    更新日期：2015-08-01 00:00:00

  • A carbonate-forming Baeyer-Villiger monooxygenase.

    abstract：:Despite the remarkable versatility displayed by flavin-dependent monooxygenases (FMOs) in natural product biosynthesis, one notably missing activity is the oxidative generation of carbonate functional groups. We describe a multifunctional Baeyer-Villiger monooxygenase, CcsB, which catalyzes the formation of an in-line...

    journal_title：Nature chemical biology

    pub_type： 杂志文章

    doi：10.1038/nchembio.1527

    authors： Hu Y,Dietrich D,Xu W,Patel A,Thuss JA,Wang J,Yin WB,Qiao K,Houk KN,Vederas JC,Tang Y

    更新日期：2014-07-01 00:00:00

  • Cholesterol modulates glycolipid conformation and receptor activity.

    abstract：:We document a new dimension of surface recognition in which communication is controlled through the collective behavior of lipids. Membrane cholesterol induces a tilt in glycolipid receptor headgroup, resulting in loss of access for ligand binding. This property appears to organize erythrocyte blood group presentation...

    journal_title：Nature chemical biology

    pub_type： 杂志文章

    doi：10.1038/nchembio.551

    authors： Lingwood D,Binnington B,Róg T,Vattulainen I,Grzybek M,Coskun U,Lingwood CA,Simons K

    更新日期：2011-05-01 00:00:00

  • Small-molecule-based regulation of RNA-delivered circuits in mammalian cells.

    abstract：:Synthetic mRNA is an attractive vehicle for gene therapies because of its transient nature and improved safety profile over DNA. However, unlike DNA, broadly applicable methods to control expression from mRNA are lacking. Here we describe a platform for small-molecule-based regulation of expression from modified RNA (...

    journal_title：Nature chemical biology

    pub_type： 杂志文章

    doi：10.1038/s41589-018-0146-9

    authors： Wagner TE,Becraft JR,Bodner K,Teague B,Zhang X,Woo A,Porter E,Alburquerque B,Dobosh B,Andries O,Sanders NN,Beal J,Densmore D,Kitada T,Weiss R

    更新日期：2018-11-01 00:00:00

  • Decoding without the cipher.

    abstract：: ...

    journal_title：Nature chemical biology

    pub_type： 评论,杂志文章

    doi：10.1038/s41589-019-0230-9

    authors： Singh Gautam AK,Matouschek A

    更新日期：2019-03-01 00:00:00

  • A fluorescent probe for cysteine depalmitoylation reveals dynamic APT signaling.

    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

    authors： Kathayat RS,Elvira PD,Dickinson BC

    更新日期：2017-02-01 00:00:00

  • Modulating the DNA polymerase β reaction equilibrium to dissect the reverse reaction.

    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

    authors： Shock DD,Freudenthal BD,Beard WA,Wilson SH

    更新日期：2017-10-01 00:00:00