当前位置： SCI文献检索 > PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA期刊下所有文献 > Hijacking a hydroxyethyl unit from a central metabolic ketose into a nonribosomal peptide assembly line.

Hijacking a hydroxyethyl unit from a central metabolic ketose into a nonribosomal peptide assembly line.

Abstract：

:Nonribosomal peptide synthetases (NRPSs) usually catalyze the biosynthesis of peptide natural products by sequential selection, activation, and condensation of amino acid precursors. It was reported that some fatty acids, α-ketoacids, and α-hydroxyacids originating from amino acid metabolism as well as polyketide-derived units can also be used by NRPS assembly lines as an alternative to amino acids. Ecteinascidin 743 (ET-743), naphthyridinomycin (NDM), and quinocarcin (QNC) are three important antitumor natural products belonging to the tetrahydroisoquinoline family. Although ET-743 has been approved as an anticancer drug, the origin of an identical two-carbon (C(2)) fragment among these three antibiotics has not been elucidated despite much effort in the biosynthetic research in the past 30 y. Here we report that two unexpected two-component transketolases (TKases), NapB/NapD in the NDM biosynthetic pathway and QncN/QncL in QNC biosynthesis, catalyze the transfer of a glycolaldehyde unit from ketose to the lipoyl group to yield the glycolicacyl lipoic acid intermediate and then transfer the C(2) unit to an acyl carrier protein (ACP) to form glycolicacyl-S-ACP as an extender unit for NRPS. Our results demonstrate a unique NRPS extender unit directly derived from ketose phosphates through (α,β-dihydroxyethyl)-thiamin diphosphate and a lipoyl group-tethered ester intermediate catalyzed by the TKase-ACP platform in the context of NDM and QNC biosynthesis, all of which also highlights the biosynthesis of ET-743. This hybrid system and precursor are distinct from the previously described universal modes involving the NRPS machinery. They exemplify an alternate strategy in hybrid NRPS biochemistry and enrich the diversity of precursors for NRPS combinatorial biosynthesis.

journal_name

Proc Natl Acad Sci U S A

journal_title

Proceedings of the National Academy of Sciences of the United States of America

authors

Peng C,Pu JY,Song LQ,Jian XH,Tang MC,Tang GL

doi

10.1073/pnas.1204232109

subject

Has Abstract

pub_date

2012-05-29 00:00:00

pages

8540-5

issue

22

eissn

0027-8424

issn

1091-6490

pii

1204232109

journal_volume

109

pub_type

杂志文章

相关文献

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA文献大全
  • KaiA-stimulated KaiC phosphorylation in circadian timing loops in cyanobacteria.

    abstract：:Cyanobacterial clock proteins KaiA and KaiC are proposed as positive and negative regulators in the autoregulatory circadian kaiBC expression, respectively. Here, we show that activation of kaiBC expression by kaiA requires KaiC, suggesting a positive feedback control in the cyanobacterial clockwork. We found that rob...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.222467299

    authors： Iwasaki H,Nishiwaki T,Kitayama Y,Nakajima M,Kondo T

    更新日期：2002-11-26 00:00:00

  • Antibodies mediate intracellular immunity through tripartite motif-containing 21 (TRIM21).

    abstract：:Antibodies provide effective antiviral immunity despite the fact that viruses escape into cells when they infect. Here we show that antibodies remain attached to viruses after cell infection and mediate an intracellular immune response that disables virions in the cytosol. We have discovered that cells possess a cytos...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.1014074107

    authors： Mallery DL,McEwan WA,Bidgood SR,Towers GJ,Johnson CM,James LC

    更新日期：2010-11-16 00:00:00

  • Thymic tumorigenesis induced by overexpression of p56lck.

    abstract：:The lck gene encodes a membrane-associated protein tyrosine kinase (p56lck) that is believed to participate in lymphocyte-specific signal transduction pathways. To investigate the function of this molecule, transgenic mice were generated carrying the wild-type lck gene or a mutated lck gene encoding a constitutively a...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.88.9.3977

    authors： Abraham KM,Levin SD,Marth JD,Forbush KA,Perlmutter RM

    更新日期：1991-05-01 00:00:00

  • Different personal propensities among scientists relate to deeper vs. broader knowledge contributions.

    abstract：:Scientific journal publications, and their contributions to knowledge, can be described by their depth (specialized, domain-specific knowledge extensions) and breadth (topical scope, including spanning multiple knowledge domains). Toward generating hypotheses about how scientists' personal dispositions would uniquely ...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.1421286112

    authors： Bateman TS,Hess AM

    更新日期：2015-03-24 00:00:00

  • Quantitative genomic analysis of RecA protein binding during DNA double-strand break repair reveals RecBCD action in vivo.

    abstract：:Understanding molecular mechanisms in the context of living cells requires the development of new methods of in vivo biochemical analysis to complement established in vitro biochemistry. A critically important molecular mechanism is genetic recombination, required for the beneficial reassortment of genetic information...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.1424269112

    authors： Cockram CA,Filatenkova M,Danos V,El Karoui M,Leach DR

    更新日期：2015-08-25 00:00:00

  • The induced prostaglandin E2 pathway is a key regulator of the respiratory response to infection and hypoxia in neonates.

    abstract：:Infection during the neonatal period commonly induces apnea episodes, and the proinflammatory cytokine IL-1beta may serve as a critical mediator between these events. To determine the mechanism by which IL-1beta depresses respiration, we examined a prostaglandin E(2) (PGE(2))-dependent pathway in newborn mice and huma...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.0611468104

    authors： Hofstetter AO,Saha S,Siljehav V,Jakobsson PJ,Herlenius E

    更新日期：2007-06-05 00:00:00

  • Critical point for Bose-Einstein condensation of excitons in graphite.

    abstract：:An exciton is an electron-hole pair bound by attractive Coulomb interaction. Short-lived excitons have been detected by a variety of experimental probes in numerous contexts. An excitonic insulator, a collective state of such excitons, has been more elusive. Here, thanks to Nernst measurements in pulsed magnetic field...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.2012811117

    authors： Wang J,Nie P,Li X,Zuo H,Fauqué B,Zhu Z,Behnia K

    更新日期：2020-12-01 00:00:00

  • Insulin growth factor signaling is regulated by microRNA-486, an underexpressed microRNA in lung cancer.

    abstract：:MicroRNAs (miRNAs) are small 19- to 24-nt noncoding RNAs that have the capacity to regulate fundamental biological processes essential for cancer initiation and progression. In cancer, miRNAs may function as oncogenes or tumor suppressors. Here, we conducted global profiling for miRNAs in a cohort of stage 1 nonsmall ...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.1307107110

    authors： Peng Y,Dai Y,Hitchcock C,Yang X,Kassis ES,Liu L,Luo Z,Sun HL,Cui R,Wei H,Kim T,Lee TJ,Jeon YJ,Nuovo GJ,Volinia S,He Q,Yu J,Nana-Sinkam P,Croce CM

    更新日期：2013-09-10 00:00:00

  • The progesterone antagonist RU486 acquires agonist activity upon stimulation of cAMP signaling pathways.

    abstract：:The protein kinase A stimulator cAMP can potentiate the ability of progestins to induce the transactivation function of the human progesterone receptor (hPR). We questioned in the present study whether cAMP could functionally cooperate with the progestin antagonist RU486. In T47D human breast cancer cells, RU486 behav...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.90.10.4441

    authors： Beck CA,Weigel NL,Moyer ML,Nordeen SK,Edwards DP

    更新日期：1993-05-15 00:00:00

  • Linking genome and proteome by mass spectrometry: large-scale identification of yeast proteins from two dimensional gels.

    abstract：:The function of many of the uncharacterized open reading frames discovered by genomic sequencing can be determined at the level of expressed gene products, the proteome. However, identifying the cognate gene from minute amounts of protein has been one of the major problems in molecular biology. Using yeast as an examp...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.93.25.14440

    authors： Shevchenko A,Jensen ON,Podtelejnikov AV,Sagliocco F,Wilm M,Vorm O,Mortensen P,Shevchenko A,Boucherie H,Mann M

    更新日期：1996-12-10 00:00:00

  • Genotypic variation within asexual lineages of Taraxacum officinale.

    abstract：:Restriction site variation in DNA that encodes rRNA (rDNA) was surveyed among 714 offspring within 31 lineages (26 genotypes) of obligate asexually reproducing Taraxacum officinale (dandelions). Although clonal offspring are expected, plants with nonparental rDNA were produced from two parents that were themselves sib...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.87.3.998

    authors： King LM,Schaal BA

    更新日期：1990-02-01 00:00:00

  • A theoretical examination of the factors controlling the catalytic efficiency of the DNA-(adenine-N6)-methyltransferase from Thermus aquaticus.

    abstract：:Ab initio and density functional calculations have been carried out to more fully understand the factors controlling the catalytic activity of the Thermus aquaticus DNA methyltransferase (MTaqI) in the N-methylation at the N(6) of an adenine nucleobase. The noncatalyzed reaction was modeled as a methyl transfer from t...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.122231499

    authors： Newby ZE,Lau EY,Bruice TC

    更新日期：2002-06-11 00:00:00

  • Partial purification and characterization of a membrane-derived factor regulating neurotransmitter phenotypic expression.

    abstract：:Cell membrane contact induces the de novo expression of choline O-acetyltransferase (CAT; acetyl-CoA: choline O-acetyltransferase, EC 2.3.1.6) activity in cultures of virtually pure neonatal rat dissociated sympathetic neurons. To identify molecular mechanisms underlying membrane-associated CAT induction, the responsi...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.86.3.1080

    authors： Adler JE,Schleifer LS,Black IB

    更新日期：1989-02-01 00:00:00

  • The glycophorin C N-linked glycan is a critical component of the ligand for the Plasmodium falciparum erythrocyte receptor BAEBL.

    abstract：:Plasmodium vivax uses a single member of the Duffy binding-like (DBL) receptor family to invade erythrocytes and is not found in West Africa where its erythrocyte ligand, the Duffy blood group antigen, is missing. In contrast, Plasmodium falciparum expresses four members of the DBL family, and remarkably, single-point...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.0510648103

    authors： Mayer DC,Jiang L,Achur RN,Kakizaki I,Gowda DC,Miller LH

    更新日期：2006-02-14 00:00:00

  • ATRIP associates with replication protein A-coated ssDNA through multiple interactions.

    abstract：:The ATR (ATM- and rad3-related)-mediated checkpoint pathway has a crucial role in regulating the cellular responses to DNA damage and DNA-replication stress. ATRIP (ATR-interacting protein), the regulatory partner of ATR, binds directly to replication protein A (RPA)-coated ssDNA and enables the ATR-ATRIP complex to r...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.0510223103

    authors： Namiki Y,Zou L

    更新日期：2006-01-17 00:00:00

  • Protein comparison and classification: a differential geometric approach.

    abstract：:A method is proposed for rapidly, quantitatively comparing protein structures of arbitrary sizes, based on the differential geometric representation. The method is applied to a group of 22 protein x-ray structures, and the resulting network of closest relationships is delineated. Several well-known fold types are auto...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.85.3.777

    authors： Rackovsky S,Goldstein DA

    更新日期：1988-02-01 00:00:00

  • Regulation of Cl- channels in normal and cystic fibrosis airway epithelial cells by extracellular ATP.

    abstract：:The rate of Cl- secretion by human airway epithelium is determined, in part, by apical cell membrane Cl- conductance. In cystic fibrosis airway epithelia, defective regulation of Cl- conductance decreases the capability to secrete Cl-. Here we report that extracytosolic ATP in the luminal bath of cultured human airway...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.89.5.1621

    authors： Stutts MJ,Chinet TC,Mason SJ,Fullton JM,Clarke LL,Boucher RC

    更新日期：1992-03-01 00:00:00

  • Specific accumulation of tumor-derived adhesion factor in tumor blood vessels and in capillary tube-like structures of cultured vascular endothelial cells.

    abstract：:Tumor-derived adhesion factor (TAF) was previously identified as a cell adhesion molecule secreted by human bladder carcinoma cell line EJ-1. To elucidate the physiological function of TAF, we examined its distribution in human normal and tumor tissues. Immunochemical staining with an anti-TAF monoclonal antibody show...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.93.16.8384

    authors： Akaogi K,Okabe Y,Sato J,Nagashima Y,Yasumitsu H,Sugahara K,Miyazaki K

    更新日期：1996-08-06 00:00:00

  • Constitutive signaling activity of a receptor-associated protein links fertilization with embryonic patterning in Arabidopsis thaliana.

    abstract：:In flowering plants, the asymmetrical division of the zygote is the first hallmark of apical-basal polarity of the embryo and is controlled by a MAP kinase pathway that includes the MAPKKK YODA (YDA). In Arabidopsis, YDA is activated by the membrane-associated pseudokinase SHORT SUSPENSOR (SSP) through an unusual pare...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.1815866116

    authors： Neu A,Eilbert E,Asseck LY,Slane D,Henschen A,Wang K,Bürgel P,Hildebrandt M,Musielak TJ,Kolb M,Lukowitz W,Grefen C,Bayer M

    更新日期：2019-03-19 00:00:00

  • Alternative processing of bovine growth hormone mRNA: nonsplicing of the final intron predicts a high molecular weight variant of bovine growth hormone.

    abstract：:We have detected a variant species of bovine growth hormone mRNA in bovine pituitary tissue and in a stably transfected bovine growth hormone-producing cell line. Analysis of this variant mRNA indicated that the last intervening sequence (intron D) had not been removed by splicing. Inspection of the sequence of intron...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.84.9.2673

    authors： Hampson RK,Rottman FM

    更新日期：1987-05-01 00:00:00

  • Cellular and humoral immune responses to adenoviral vectors containing factor IX gene: tolerization of factor IX and vector antigens allows for long-term expression.

    abstract：:Recombinant adenoviruses containing the canine factor IX (FIX) cDNA were directly introduced in the hind leg muscle of mice. We show that (i) in nude mice, high expression (1-5 micrograms/ml in plasma) of FIX protein can be detected for > 300 days; (ii) in contrast, expression of FIX protein was transient (7-10 days) ...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.92.5.1401

    authors： Dai Y,Schwarz EM,Gu D,Zhang WW,Sarvetnick N,Verma IM

    更新日期：1995-02-28 00:00:00

  • Identification of a genetic cluster influencing memory performance and hippocampal activity in humans.

    abstract：:Experimental work in animals has shown that memory formation depends on a cascade of molecular events. Here we show that variability of human memory performance is related to variability in genes encoding proteins of this signaling cascade, including the NMDA and metabotrobic glutamate receptors, adenylyl cyclase, CAM...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.0510212103

    authors： de Quervain DJ,Papassotiropoulos A

    更新日期：2006-03-14 00:00:00

  • Acetyl-L-carnitine fed to old rats partially restores mitochondrial function and ambulatory activity.

    abstract：:Mitochondrial function and ambulatory activity were monitored after feeding old rats acetyl-L-carnitine (ALCAR). Young (3-5 mo) and old (22-28 mo) rats were given a 1.5% (wt/vol) solution of ALCAR in their drinking water for 1 mo, were sacrificed, and their liver parenchymal cells were isolated. ALCAR supplementation ...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.95.16.9562

    authors： Hagen TM,Ingersoll RT,Wehr CM,Lykkesfeldt J,Vinarsky V,Bartholomew JC,Song MH,Ames BN

    更新日期：1998-08-04 00:00:00

  • Antiestrogen ICI 164,384 reduces cellular estrogen receptor content by increasing its turnover.

    abstract：:The ability of estrogens to stimulate the transcriptional activity of the estrogen receptor can be inhibited by a diverse range of estrogen antagonists. Here we show that the antiestrogen ICI 164,384, N-(n-butyl)-11-[3,17 beta-dihydroxy-estra-1,3,5(10)-trien-7 alpha-yl]N-methylundecanamide, rapidly reduces the levels ...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.89.9.4037

    authors： Dauvois S,Danielian PS,White R,Parker MG

    更新日期：1992-05-01 00:00:00

  • Identification of genes that synergize with Cbfb-MYH11 in the pathogenesis of acute myeloid leukemia.

    abstract：:Acute myeloid leukemia subtype M4 with eosinophilia is associated with a chromosome 16 inversion that creates a fusion gene CBFB-MYH11. We have previously shown that CBFB-MYH11 is necessary but not sufficient for leukemogenesis. Here, we report the identification of genes that specifically cooperate with CBFB-MYH11 in...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.0400930101

    authors： Castilla LH,Perrat P,Martinez NJ,Landrette SF,Keys R,Oikemus S,Flanegan J,Heilman S,Garrett L,Dutra A,Anderson S,Pihan GA,Wolff L,Liu PP

    更新日期：2004-04-06 00:00:00

  • Biochemical evolution III: polymerization on organophilic silica-rich surfaces, crystal-chemical modeling, formation of first cells, and geological clues.

    abstract：:Catalysis at organophilic silica-rich surfaces of zeolites and feldspars might generate replicating biopolymers from simple chemicals supplied by meteorites, volcanic gases, and other geological sources. Crystal-chemical modeling yielded packings for amino acids neatly encapsulated in 10-ring channels of the molecular...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章,评审

    doi：10.1073/pnas.96.7.3479

    authors： Smith JV,Arnold FP Jr,Parsons I,Lee MR

    更新日期：1999-03-30 00:00:00

  • Use of site-directed mutagenesis to enhance the epitope-shielding effect of covalent modification of proteins with polyethylene glycol.

    abstract：:Modification by covalent attachment of polyethylene glycol (PEG) can reduce the immunogenicity and prolong the circulating life of proteins, but the utility of this approach for any protein is restricted by the number and distribution of PEG attachment sites (e.g., epsilon-amino groups of lysine residues). We have dev...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.88.16.7185

    authors： Hershfield MS,Chaffee S,Koro-Johnson L,Mary A,Smith AA,Short SA

    更新日期：1991-08-15 00:00:00

  • Elevated DNA topoisomerase II activity in nitrogen mustard-resistant human cells.

    abstract：:A human Burkitt lymphoma cell line, Raji-HN2, made 10-fold more resistant to nitrogen mustard (HN2) than the parental Raji cell line, exhibited the following characteristics when compared to the parental Raji cells: (i) decreased HN2-induced DNA interstrand crosslinking; (ii) increased (3-fold) DNA topoisomerase II [D...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.84.21.7668

    authors： Tan KB,Mattern MR,Boyce RA,Schein PS

    更新日期：1987-11-01 00:00:00

  • A putative ATP-dependent RNA helicase involved in Saccharomyces cerevisiae ribosome assembly.

    abstract：:We have isolated a cold-sensitive mutant of Saccharomyces cerevisiae in which there is a deficit of 60S ribosomal subunits. Cold sensitivity and the assembly defect are recessive and cosegregate, defining a single essential gene that we designated DRS1 (deficiency of ribosomal subunits). The wild-type DRS1 gene was cl...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.89.23.11131

    authors： Ripmaster TL,Vaughn GP,Woolford JL Jr

    更新日期：1992-12-01 00:00:00

  • Extracting multistage screening rules from online dating activity data.

    abstract：:This paper presents a statistical framework for harnessing online activity data to better understand how people make decisions. Building on insights from cognitive science and decision theory, we develop a discrete choice model that allows for exploratory behavior and multiple stages of decision making, with different...

    journal_title：Proceedings of the National Academy of Sciences of the United States of America

    pub_type： 杂志文章

    doi：10.1073/pnas.1522494113

    authors： Bruch E,Feinberg F,Lee KY

    更新日期：2016-09-20 00:00:00