A crotonyl-CoA reductase-carboxylase independent pathway for assembly of unusual alkylmalonyl-CoA polyketide synthase extender units.

Abstract:

:Type I modular polyketide synthases assemble diverse bioactive natural products. Such multienzymes typically use malonyl and methylmalonyl-CoA building blocks for polyketide chain assembly. However, in several cases more exotic alkylmalonyl-CoA extender units are also known to be incorporated. In all examples studied to date, such unusual extender units are biosynthesized via reductive carboxylation of α, β-unsaturated thioesters catalysed by crotonyl-CoA reductase/carboxylase (CCRC) homologues. Here we show using a chemically-synthesized deuterium-labelled mechanistic probe, and heterologous gene expression experiments that the unusual alkylmalonyl-CoA extender units incorporated into the stambomycin family of polyketide antibiotics are assembled by direct carboxylation of medium chain acyl-CoA thioesters. X-ray crystal structures of the unusual β-subunit of the acyl-CoA carboxylase (YCC) responsible for this reaction, alone and in complex with hexanoyl-CoA, reveal the molecular basis for substrate recognition, inspiring the development of methodology for polyketide bio-orthogonal tagging via incorporation of 6-azidohexanoic acid and 8-nonynoic acid into novel stambomycin analogues.

journal_name

Nat Commun

journal_title

Nature communications

authors

Ray L,Valentic TR,Miyazawa T,Withall DM,Song L,Milligan JC,Osada H,Takahashi S,Tsai SC,Challis GL

doi

10.1038/ncomms13609

subject

Has Abstract

pub_date

2016-12-21 00:00:00

pages

13609

issn

2041-1723

pii

ncomms13609

journal_volume

7

pub_type

杂志文章
  • Tuning charge and correlation effects for a single molecule on a graphene device.

    abstract::The ability to understand and control the electronic properties of individual molecules in a device environment is crucial for developing future technologies at the nanometre scale and below. Achieving this, however, requires the creation of three-terminal devices that allow single molecules to be both gated and image...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms13553

    authors: Wickenburg S,Lu J,Lischner J,Tsai HZ,Omrani AA,Riss A,Karrasch C,Bradley A,Jung HS,Khajeh R,Wong D,Watanabe K,Taniguchi T,Zettl A,Neto AHC,Louie SG,Crommie MF

    更新日期:2016-11-25 00:00:00

  • The telomere binding protein Pot1 maintains haematopoietic stem cell activity with age.

    abstract::Repeated cell divisions and aging impair stem cell function. However, the mechanisms by which this occurs are not fully understood. Here we show that protection of telomeres 1A (Pot1a), a component of the Shelterin complex that protects telomeres, improves haematopoietic stem cell (HSC) activity during aging. Pot1a is...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-017-00935-4

    authors: Hosokawa K,MacArthur BD,Ikushima YM,Toyama H,Masuhiro Y,Hanazawa S,Suda T,Arai F

    更新日期:2017-10-06 00:00:00

  • In situ supramolecular polymerization-enhanced self-assembly of polymer vesicles for highly efficient photothermal therapy.

    abstract::Vesicular photothermal therapy agents (PTAs) are highly desirable in photothermal therapy (PTT) for their excellent light-harvesting ability and versatile hollow compartments. However, up to now, the reported vesicular PTAs are generally self-assembled from small molecules like liposomes, and polymer vesicles have sel...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-15427-1

    authors: Liu Y,Wang H,Li S,Chen C,Xu L,Huang P,Liu F,Su Y,Qi M,Yu C,Zhou Y

    更新日期:2020-04-07 00:00:00

  • Elucidation of the biosynthesis of carnosic acid and its reconstitution in yeast.

    abstract::Rosemary extracts containing the phenolic diterpenes carnosic acid and its derivative carnosol are approved food additives used in an increasingly wide range of products to enhance shelf-life, thanks to their high anti-oxidant activity. We describe here the elucidation of the complete biosynthetic pathway of carnosic ...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms12942

    authors: Scheler U,Brandt W,Porzel A,Rothe K,Manzano D,Božić D,Papaefthimiou D,Balcke GU,Henning A,Lohse S,Marillonnet S,Kanellis AK,Ferrer A,Tissier A

    更新日期:2016-10-05 00:00:00

  • Ballistic interferences in suspended graphene.

    abstract::The low-energy electronic excitations in graphene are described by massless Dirac fermions that have a linear dispersion relation. Taking advantage of this 'optics-like' electron dynamics, generic optical elements like lenses and wave guides have been proposed for electrons in graphene. Tuning of these elements relies...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms3342

    authors: Rickhaus P,Maurand R,Liu MH,Weiss M,Richter K,Schönenberger C

    更新日期:2013-01-01 00:00:00

  • Publisher Correction: Z-ring membrane anchors associate with cell wall synthases to initiate bacterial cell division.

    abstract::The original version of this Article contained errors in Figures 1 and 3. In Fig. 1b, the label 'IP-PBP3' above the second of the three blots incorrectly read 'IP-PBP1B'. In Fig. 3b, the label 'PBP1B' under the first bar of each chart incorrectly read 'PBP1A'. These errors have been corrected in both the PDF and HTML ...

    journal_title:Nature communications

    pub_type: 杂志文章,已发布勘误

    doi:10.1038/s41467-019-08410-y

    authors: Pazos M,Peters K,Casanova M,Palacios P,VanNieuwenhze M,Breukink E,Vicente M,Vollmer W

    更新日期:2019-01-30 00:00:00

  • Transcriptomic signatures of NK cells suggest impaired responsiveness in HIV-1 infection and increased activity post-vaccination.

    abstract::Natural killer (NK) cells limit viral replication by direct recognition of infected cells, antibody-dependent cellular cytotoxicity (ADCC), and releasing cytokines. Although growing evidence supports NK cell antiviral immunity in HIV-1 infection, further knowledge of their response is necessary. Here we show that NK c...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-018-03618-w

    authors: Costanzo MC,Kim D,Creegan M,Lal KG,Ake JA,Currier JR,Streeck H,Robb ML,Michael NL,Bolton DL,Steers NJ,Eller MA

    更新日期:2018-03-23 00:00:00

  • Embracing the dropouts in single-cell RNA-seq analysis.

    abstract::One primary reason that makes single-cell RNA-seq analysis challenging is dropouts, where the data only captures a small fraction of the transcriptome of each cell. Almost all computational algorithms developed for single-cell RNA-seq adopted gene selection, dimension reduction or imputation to address the dropouts. H...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-14976-9

    authors: Qiu P

    更新日期:2020-03-03 00:00:00

  • Absorption-induced scattering and surface plasmon out-coupling from absorber-coated plasmonic metasurfaces.

    abstract::Interactions between absorbers and plasmonic metasurfaces can give rise to unique optical properties not present for either of the individual materials and can influence the performance of a host of optical sensing and thin-film optoelectronic applications. Here we identify three distinct mode types of absorber-coated...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms8899

    authors: Petoukhoff CE,O'Carroll DM

    更新日期:2015-08-14 00:00:00

  • PLCγ-dependent mTOR signalling controls IL-7-mediated early B cell development.

    abstract::The precise molecular mechanism underlying the regulation of early B cell lymphopoiesis is unclear. The PLCγ signaling pathway is critical for antigen receptor-mediated lymphocyte activation, but its function in cytokine signaling is unknown. Here we show that PLCγ1/PLCγ2 double deficiency in mice blocks early B cell ...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-017-01388-5

    authors: Yu M,Chen Y,Zeng H,Zheng Y,Fu G,Zhu W,Broeckel U,Aggarwal P,Turner A,Neale G,Guy C,Zhu N,Chi H,Wen R,Wang D

    更新日期:2017-11-13 00:00:00

  • Publisher Correction: Migration alters oscillatory dynamics and promotes survival in connected bacterial populations.

    abstract::In the original version of this Article, an additional double-headed arrow was inadvertently included within Fig. 3e. This error has been corrected in both the PDF and HTML versions of the Article. ...

    journal_title:Nature communications

    pub_type: 杂志文章,已发布勘误

    doi:10.1038/s41467-019-08615-1

    authors: Gokhale S,Conwill A,Ranjan T,Gore J

    更新日期:2019-02-12 00:00:00

  • A co-design framework of neural networks and quantum circuits towards quantum advantage.

    abstract::Despite the pursuit of quantum advantages in various applications, the power of quantum computers in executing neural network has mostly remained unknown, primarily due to a missing tool that effectively designs a neural network suitable for quantum circuit. Here, we present a neural network and quantum circuit co-des...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-20729-5

    authors: Jiang W,Xiong J,Shi Y

    更新日期:2021-01-25 00:00:00

  • A rare functional cardioprotective APOC3 variant has risen in frequency in distinct population isolates.

    abstract::Isolated populations can empower the identification of rare variation associated with complex traits through next generation association studies, but the generalizability of such findings remains unknown. Here we genotype 1,267 individuals from a Greek population isolate on the Illumina HumanExome Beadchip, in search ...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms3872

    authors: Tachmazidou I,Dedoussis G,Southam L,Farmaki AE,Ritchie GR,Xifara DK,Matchan A,Hatzikotoulas K,Rayner NW,Chen Y,Pollin TI,O'Connell JR,Yerges-Armstrong LM,Kiagiadaki C,Panoutsopoulou K,Schwartzentruber J,Moutsianas L,UK1

    更新日期:2013-01-01 00:00:00

  • Ultrahigh drive current and large selectivity in GeS selector.

    abstract::Selector devices are indispensable components of large-scale nonvolatile memory and neuromorphic array systems. Besides the conventional silicon transistor, two-terminal ovonic threshold switching device with much higher scalability is currently the most industrially favored selector technology. However, current ovoni...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-18382-z

    authors: Jia S,Li H,Gotoh T,Longeaud C,Zhang B,Lyu J,Lv S,Zhu M,Song Z,Liu Q,Robertson J,Liu M

    更新日期:2020-09-15 00:00:00

  • Serial processing of kinematic signals by cerebellar circuitry during voluntary whisking.

    abstract::Purkinje cells (PCs) in Crus 1 represent whisker movement via linear changes in firing rate, but the circuit mechanisms underlying this coding scheme are unknown. Here we examine the role of upstream inputs to PCs-excitatory granule cells (GCs) and inhibitory molecular layer interneurons-in processing of whisking sign...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-017-00312-1

    authors: Chen S,Augustine GJ,Chadderton P

    更新日期:2017-08-10 00:00:00

  • The reductive glycine pathway allows autotrophic growth of Desulfovibrio desulfuricans.

    abstract::Six CO2 fixation pathways are known to operate in photoautotrophic and chemoautotrophic microorganisms. Here, we describe chemolithoautotrophic growth of the sulphate-reducing bacterium Desulfovibrio desulfuricans (strain G11) with hydrogen and sulphate as energy substrates. Genomic, transcriptomic, proteomic and meta...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-18906-7

    authors: Sánchez-Andrea I,Guedes IA,Hornung B,Boeren S,Lawson CE,Sousa DZ,Bar-Even A,Claassens NJ,Stams AJM

    更新日期:2020-10-09 00:00:00

  • Assessment of corneal substrate biomechanics and its effect on epithelial stem cell maintenance and differentiation.

    abstract::Whilst demonstrated extensively in vitro, the control of cell behaviour via modulation of substrate compliance in live tissues has not been accomplished to date. Here we propose that stem cells can be regulated solely through in situ modulation of tissue biomechanics. By first establishing, via high-resolution Brillou...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-09331-6

    authors: Gouveia RM,Lepert G,Gupta S,Mohan RR,Paterson C,Connon CJ

    更新日期:2019-04-03 00:00:00

  • Origin of pressure-induced crystallization of Ce75Al25 metallic glass.

    abstract::Phase transitions in amorphous alloys under pressure are an important fundamental problem. Here we report on a first-principles study that reproduces the recently discovered pressure-induced crystallization of amorphous Ce100-xAlx (x<25) alloys and reveals an atomistic transformation mechanism. Contrary to common beli...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms7493

    authors: Wu M,Tse JS,Wang SY,Wang CZ,Jiang JZ

    更新日期:2015-03-09 00:00:00

  • Inactivation of NF-κB2 (p52) restrains hepatic glucagon response via preserving PDE4B induction.

    abstract::Glucagon promotes hepatic gluconeogenesis and maintains whole-body glucose levels during fasting. The regulatory factors that are involved in fasting glucagon response are not well understood. Here we report a role of p52, a key activator of the noncanonical nuclear factor-kappaB signaling, in hepatic glucagon respons...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-12351-x

    authors: Zhang WS,Pan A,Zhang X,Ying A,Ma G,Liu BL,Qi LW,Liu Q,Li P

    更新日期:2019-09-20 00:00:00

  • Wave-induced loss of ultra-relativistic electrons in the Van Allen radiation belts.

    abstract::The dipole configuration of the Earth's magnetic field allows for the trapping of highly energetic particles, which form the radiation belts. Although significant advances have been made in understanding the acceleration mechanisms in the radiation belts, the loss processes remain poorly understood. Unique observation...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms12883

    authors: Shprits YY,Drozdov AY,Spasojevic M,Kellerman AC,Usanova ME,Engebretson MJ,Agapitov OV,Zhelavskaya IS,Raita TJ,Spence HE,Baker DN,Zhu H,Aseev NA

    更新日期:2016-09-28 00:00:00

  • Macromolecular semi-rigid nanocavities for cooperative recognition of specific large molecular shapes.

    abstract::Molecular shape recognition for larger guest molecules (typically over 1 nm) is a difficult task because it requires cooperativity within a wide three-dimensional nanospace coincidentally probing every molecular aspect (size, outline shape, flexibility and specific groups). Although the intelligent functions of protei...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms3581

    authors: Imaoka T,Kawana Y,Kurokawa T,Yamamoto K

    更新日期:2013-01-01 00:00:00

  • Carbon monoxide in an extremely metal-poor galaxy.

    abstract::Extremely metal-poor galaxies with metallicity below 10% of the solar value in the local universe are the best analogues to investigating the interstellar medium at a quasi-primitive environment in the early universe. In spite of the ongoing formation of stars in these galaxies, the presence of molecular gas (which is...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms13789

    authors: Shi Y,Wang J,Zhang ZY,Gao Y,Hao CN,Xia XY,Gu Q

    更新日期:2016-12-09 00:00:00

  • Unusually efficient photocurrent extraction in monolayer van der Waals heterostructure by tunnelling through discretized barriers.

    abstract::Two-dimensional layered transition-metal dichalcogenides have attracted considerable interest for their unique layer-number-dependent properties. In particular, vertical integration of these two-dimensional crystals to form van der Waals heterostructures can open up a new dimension for the design of functional electro...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms13278

    authors: Yu WJ,Vu QA,Oh H,Nam HG,Zhou H,Cha S,Kim JY,Carvalho A,Jeong M,Choi H,Castro Neto AH,Lee YH,Duan X

    更新日期:2016-11-09 00:00:00

  • Promotion of oxygen reduction by a bio-inspired tethered iron phthalocyanine carbon nanotube-based catalyst.

    abstract::Electrocatalysts for oxygen reduction are a critical component that may dramatically enhance the performance of fuel cells and metal-air batteries, which may provide the power for future electric vehicles. Here we report a novel bio-inspired composite electrocatalyst, iron phthalocyanine with an axial ligand anchored ...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms3076

    authors: Cao R,Thapa R,Kim H,Xu X,Gyu Kim M,Li Q,Park N,Liu M,Cho J

    更新日期:2013-01-01 00:00:00

  • FAK-heterozygous mice display enhanced tumour angiogenesis.

    abstract::Genetic ablation of endothelial focal adhesion kinase (FAK) can inhibit pathological angiogenesis, suggesting that loss of endothelial FAK is sufficient to reduce neovascularization. Here we show that reduced stromal FAK expression in FAK-heterozygous mice unexpectedly enhances both B16F0 and CMT19T tumour growth and ...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms3020

    authors: Kostourou V,Lechertier T,Reynolds LE,Lees DM,Baker M,Jones DT,Tavora B,Ramjaun AR,Birdsey GM,Robinson SD,Parsons M,Randi AM,Hart IR,Hodivala-Dilke K

    更新日期:2013-01-01 00:00:00

  • Hair cell force generation does not amplify or tune vibrations within the chicken basilar papilla.

    abstract::Frequency tuning within the auditory papilla of most non-mammalian species is electrical, deriving from ion-channel resonance within their sensory hair cells. In contrast, tuning within the mammalian cochlea is mechanical, stemming from active mechanisms within outer hair cells that amplify the basilar membrane travel...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms13133

    authors: Xia A,Liu X,Raphael PD,Applegate BE,Oghalai JS

    更新日期:2016-10-31 00:00:00

  • African-centric TP53 variant increases iron accumulation and bacterial pathogenesis but improves response to malaria toxin.

    abstract::A variant at amino acid 47 in human TP53 exists predominantly in individuals of African descent. P47S human and mouse cells show increased cancer risk due to defective ferroptosis. Here, we show that this ferroptotic defect causes iron accumulation in P47S macrophages. This high iron content alters macrophage cytokine...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-14151-9

    authors: Singh KS,Leu JI,Barnoud T,Vonteddu P,Gnanapradeepan K,Lin C,Liu Q,Barton JC,Kossenkov AV,George DL,Murphy ME,Dotiwala F

    更新日期:2020-01-24 00:00:00

  • Cervical epithelial damage promotes Ureaplasma parvum ascending infection, intrauterine inflammation and preterm birth induction in mice.

    abstract::Around 40% of preterm births are attributed to ascending intrauterine infection, and Ureaplasma parvum (UP) is commonly isolated in these cases. Here we present a mouse model of ascending UP infection that resembles human disease, using vaginal inoculation combined with mild cervical injury induced by a common spermic...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-14089-y

    authors: Pavlidis I,Spiller OB,Sammut Demarco G,MacPherson H,Howie SEM,Norman JE,Stock SJ

    更新日期:2020-01-10 00:00:00

  • High-performance reconstruction of microscopic force fields from Brownian trajectories.

    abstract::The accurate measurement of microscopic force fields is crucial in many branches of science and technology, from biophotonics and mechanobiology to microscopy and optomechanics. These forces are often probed by analysing their influence on the motion of Brownian particles. Here we introduce a powerful algorithm for mi...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-018-07437-x

    authors: Pérez García L,Donlucas Pérez J,Volpe G,V Arzola A,Volpe G

    更新日期:2018-12-04 00:00:00

  • 5D operando tomographic diffraction imaging of a catalyst bed.

    abstract::We report the results from the first 5D tomographic diffraction imaging experiment of a complex Ni-Pd/CeO2-ZrO2/Al2O3 catalyst used for methane reforming. This five-dimensional (three spatial, one scattering and one dimension to denote time/imposed state) approach enabled us to track the chemical evolution of many par...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-018-07046-8

    authors: Vamvakeros A,Jacques SDM,Di Michiel M,Matras D,Middelkoop V,Ismagilov IZ,Matus EV,Kuznetsov VV,Drnec J,Senecal P,Beale AM

    更新日期:2018-11-12 00:00:00