A key developmental regulator controls the synthesis of the antibiotic erythromycin in Saccharopolyspora erythraea.

Abstract:

:Saccharopolyspora erythraea makes erythromycin, an antibiotic commonly used in human medicine. Unusually, the erythromycin biosynthetic (ery) cluster lacks a pathway-specific regulatory gene. We isolated a transcriptional regulator of the ery biosynthetic genes from S. erythraea and found that this protein appears to directly link morphological changes caused by impending starvation to the synthesis of a molecule that kills other bacteria, i.e., erythromycin. DNA binding assays, liquid and affinity chromatography, MALDI-MS analysis, and de novo sequencing identified this protein (M(r) = 18 kDa) as the S. erythraea ortholog of BldD, a key regulator of development in Streptomyces coelicolor. Recombinant S. erythraea BldD bound to all five regions containing promoters in the ery cluster as well as to its own promoter, the latter with an order-of-magnitude stronger than to the ery promoters. Deletion of bldD in S. erythraea decreased the erythromycin titer in a liquid culture 7-fold and blocked differentiation on a solid medium. Moreover, an industrial strain of S. erythraea with a higher titer of erythromycin expressed more BldD than a wild-type strain during erythromycin synthesis. Together, these results suggest that BldD concurrently regulates the synthesis of erythromycin and morphological differentiation. The ery genes are the first direct targets of a BldD ortholog to be identified that are positively regulated.

authors

Chng C,Lum AM,Vroom JA,Kao CM

doi

10.1073/pnas.0803622105

subject

Has Abstract

pub_date

2008-08-12 00:00:00

pages

11346-51

issue

32

eissn

0027-8424

issn

1091-6490

pii

0803622105

journal_volume

105

pub_type

杂志文章
  • Analysis of masked mutations in familial adenomatous polyposis.

    abstract::Familial adenomatous polyposis (FAP) is an autosomal-dominant disease characterized by the development of hundreds of adenomatous polyps of the colorectum. Approximately 80% of FAP patients can be shown to have truncating mutations of the APC gene. To determine the cause of FAP in the other 20% of patients, MAMA (mono...

    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.96.5.2322

    authors: Laken SJ,Papadopoulos N,Petersen GM,Gruber SB,Hamilton SR,Giardiello FM,Brensinger JD,Vogelstein B,Kinzler KW

    更新日期:1999-03-02 00:00:00

  • Transforming function of proto-ras genes depends on heterologous promoters and is enhanced by specific point mutations.

    abstract::Based on transfection into cells in culture or natural transduction into retroviruses, proto-ras genes seem to derive transforming function either from heterologous promoters or from point mutations. Here we ask how such different events could achieve the same results. To identify homologous regulatory elements, about...

    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.88.6.2217

    authors: Chakraborty AK,Cichutek K,Duesberg PH

    更新日期:1991-03-15 00:00:00

  • phiX174 DNA-dependent DNA synthesis in vitro: requirement for P1 ban protein in dnaB mutant extracts of Escherichia coli.

    abstract::Ammonium sulfate fractionation of crude extracts of E. coli yields a soluble enzyme fraction (about 25-fold purification) that catalyzes the conversion of phiX174 single-stranded DNA to duplex DNA. The reaction is rifampicin-resistant, requires single-stranded DNA, Mg++, deoxynucleoside triphosphates, and ATP, and is ...

    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.72.10.3907

    authors: Schuster H,Mikolajczyk M,Rohrschneider J,Geschke B

    更新日期:1975-10-01 00:00:00

  • Motor training compensates for cerebellar dysfunctions caused by oligodendrocyte ablation.

    abstract::The role played by oligodendrocytes (OLs), the myelinating cells of the CNS, during brain development has not been fully explored. We have addressed this question by inducing a temporal and reversible ablation of OLs on postnatal CNS development. OL ablation in newborn mice leads to a profound alteration in the struct...

    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.0305994101

    authors: Collin L,Usiello A,Erbs E,Mathis C,Borrelli E

    更新日期:2004-01-06 00:00:00

  • Men's status and reproductive success in 33 nonindustrial societies: Effects of subsistence, marriage system, and reproductive strategy.

    abstract::Social status motivates much of human behavior. However, status may have been a relatively weak target of selection for much of human evolution if ancestral foragers tended to be more egalitarian. We test the "egalitarianism hypothesis" that status has a significantly smaller effect on reproductive success (RS) in for...

    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.1606800113

    authors: von Rueden CR,Jaeggi AV

    更新日期:2016-09-27 00:00:00

  • Classical conditioning of analgesic and hyperalgesic pain responses without conscious awareness.

    abstract::Pain reduction and enhancement can be produced by means of conditioning procedures, yet the role of awareness during the acquisition stage of classical conditioning is unknown. We used psychophysical measures to establish whether conditioned analgesic and hyperalgesic responses could be acquired by unseen (subliminall...

    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.1504567112

    authors: Jensen K,Kirsch I,Odmalm S,Kaptchuk TJ,Ingvar M

    更新日期:2015-06-23 00:00:00

  • ZNF263 is a transcriptional regulator of heparin and heparan sulfate biosynthesis.

    abstract::Heparin is the most widely prescribed biopharmaceutical in production globally. Its potent anticoagulant activity and safety makes it the drug of choice for preventing deep vein thrombosis and pulmonary embolism. In 2008, adulterated material was introduced into the heparin supply chain, resulting in several hundred 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.1920880117

    authors: Weiss RJ,Spahn PN,Toledo AG,Chiang AWT,Kellman BP,Li J,Benner C,Glass CK,Gordts PLSM,Lewis NE,Esko JD

    更新日期:2020-04-28 00:00:00

  • Dopamine- and cAMP-regulated phosphoprotein (DARPP-32) and dopamine DA1 agonist-sensitive Na+,K+-ATPase in renal tubule cells.

    abstract::The cellular localization of DARPP-32, a dopamine- and cAMP-regulated phosphoprotein of Mr 32,000 that appears to mediate certain actions of dopamine in the mammalian brain by acting as an inhibitor of protein phosphatase 1, was studied in the kidney of several species. DARPP-32 mRNA and DARPP-32-like immunoreactivity...

    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.86.20.8068

    authors: Meister B,Fryckstedt J,Schalling M,Cortés R,Hökfelt T,Aperia A,Hemmings HC Jr,Nairn AC,Ehrlich M,Greengard P

    更新日期:1989-10-01 00:00:00

  • Thymosin corrects the abnormal DNA synthetic response of NZB mouse thymocytes.

    abstract::New Zealand Black (NZB) mice develop after 16 weeks of age an autoimmune and lymphoproliferative disease which is a model for systemic lupus erythematosus and lymphoid malignancy in humans. At this age, the mice manifest a progressive decline in T lymphocyte (thymus-derived lymphocyte) functions and serum thymosin lev...

    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.71.7.2637

    authors: Dauphinee MJ,Talal N,Goldstein AL,White A

    更新日期:1974-07-01 00:00:00

  • (2'-5')Oligoadenylate in rat liver: modulation after partial hepatectomy.

    abstract::(2'-5')Oligoadenylate synthetase [(2'-5')A synthetase], which synthesizes a series of oligoadenylates ppp-(A2'p)n5'A [collectively referred to as (2'-5')A], has been described previously in rat liver cells, where its concentration varied with the growth status of this organ--i.e., it decreased during the early phase o...

    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.80.15.4609

    authors: Etienne-Smekens M,Vandenbussche P,Content J,Dumont JE

    更新日期:1983-08-01 00:00:00

  • HDAC3-selective inhibitor enhances extinction of cocaine-seeking behavior in a persistent manner.

    abstract::Nonspecific histone deacetylase (HDAC) inhibition has been shown to facilitate the extinction of drug-seeking behavior in a manner resistant to reinstatement. A key open question is which specific HDAC is involved in the extinction of drug-seeking behavior. Using the selective HDAC3 inhibitor RGFP966, we investigated ...

    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.1213364110

    authors: Malvaez M,McQuown SC,Rogge GA,Astarabadi M,Jacques V,Carreiro S,Rusche JR,Wood MA

    更新日期:2013-02-12 00:00:00

  • Construction and cloning of rat albumin structural gene sequences.

    abstract::A recombinant plasmid containing a DNA segment complementary to rat liver albumin mRNA has been constructed, cloned, and used to examine the organization of albumin gene. The 18S fraction of total liver poly(A)-containing RNA was copied into a double-stranded cDNA by avian myeloblastosis virus reverse transcriptase an...

    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.76.9.4370

    authors: Kioussis D,Hamilton R,Hanson RW,Tilghman SM,Taylor JM

    更新日期:1979-09-01 00:00:00

  • Social isolation uncovers a circuit underlying context-dependent territory-covering micturition.

    abstract::The release of urine, or micturition, serves a fundamental physiological function and, in many species, is critical for social communication. In mice, the pattern of urine release is modulated by external and internal factors and transmitted to the spinal cord via the pontine micturition center (PMC). Here, we exploit...

    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.2018078118

    authors: Hyun M,Taranda J,Radeljic G,Miner L,Wang W,Ochandarena N,Huang KW,Osten P,Sabatini BL

    更新日期:2021-01-05 00:00:00

  • Loquacious-PD facilitates Drosophila Dicer-2 cleavage through interactions with the helicase domain and dsRNA.

    abstract::Loquacious-PD (Loqs-PD) is required for biogenesis of many endogenous siRNAs in Drosophila In vitro, Loqs-PD enhances the rate of dsRNA cleavage by Dicer-2 and also enables processing of substrates normally refractory to cleavage. Using purified components, and Loqs-PD truncations, we provide a mechanistic basis for L...

    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.1707063114

    authors: Trettin KD,Sinha NK,Eckert DM,Apple SE,Bass BL

    更新日期:2017-09-19 00:00:00

  • Light-driven carbon dioxide reduction to methane by nitrogenase in a photosynthetic bacterium.

    abstract::Nitrogenase is an ATP-requiring enzyme capable of carrying out multielectron reductions of inert molecules. A purified remodeled nitrogenase containing two amino acid substitutions near the site of its FeMo cofactor was recently described as having the capacity to reduce carbon dioxide (CO2) to methane (CH4). Here, we...

    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.1611043113

    authors: Fixen KR,Zheng Y,Harris DF,Shaw S,Yang ZY,Dean DR,Seefeldt LC,Harwood CS

    更新日期:2016-09-06 00:00:00

  • Noninvasive imaging of islet grafts using positron-emission tomography.

    abstract::Islet transplantation offers a potential therapy to restore glucose homeostasis in type 1 diabetes patients. However, islet transplantation is not routinely successful because most islet recipients gradually lose graft function. Furthermore, serological markers of islet function are insensitive to islet loss until the...

    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.0603909103

    authors: Lu Y,Dang H,Middleton B,Zhang Z,Washburn L,Stout DB,Campbell-Thompson M,Atkinson MA,Phelps M,Gambhir SS,Tian J,Kaufman DL

    更新日期:2006-07-25 00:00:00

  • Graded synaptic transmission at the Caenorhabditis elegans neuromuscular junction.

    abstract::Most neurotransmission is mediated by action potentials, whereas sensory neurons propagate electrical signals passively and release neurotransmitter in a graded manner. Here, we demonstrate that Caenorhabditis elegans neuromuscular junctions release neurotransmitter in a graded fashion. When motor neurons were depolar...

    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.0903570106

    authors: Liu Q,Hollopeter G,Jorgensen EM

    更新日期:2009-06-30 00:00:00

  • The priA gene encoding the primosomal replicative n' protein of Escherichia coli.

    abstract::The Escherichia coli gene encoding protein n' has been isolated and named priA for primosomal protein A. Protein n' is absolutely required for the conversion of single-stranded phi X174 DNA to the duplex replicative form in an in vitro-reconstituted system. The gene maps to 88.7 minutes on the chromosome adjacent to 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.87.12.4620

    authors: Lee EH,Masai H,Allen GC Jr,Kornberg A

    更新日期:1990-06-01 00:00:00

  • Polynucleotide ligase-catalyzed joining of deoxyribo-oligonucleotides on ribopolynucleotide templates and of ribo-oligonucleotides on deoxyribopolynucleotide templates.

    abstract::T4 polynucleotide ligase efficiently catalyzes the head-to-tail joining of the ribo-oligoadenylates, r-(pA)(8) and r-(pA)(10), in the presence of high molecular weight deoxypolythymidylate. The enzyme also catalyzes the joining of deoxy-oligothymidylates, e.g., d-(pT)(10), in the presence of ribopolyadenylate. The enz...

    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.67.1.68

    authors: Kleppe K,Van de Sande JH,Khorana HG

    更新日期:1970-09-01 00:00:00

  • ECHIDNA-mediated post-Golgi trafficking of auxin carriers for differential cell elongation.

    abstract::The plant hormone indole-acetic acid (auxin) is essential for many aspects of plant development. Auxin-mediated growth regulation typically involves the establishment of an auxin concentration gradient mediated by polarly localized auxin transporters. The localization of auxin carriers and their amount at the plasma m...

    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.1309057110

    authors: Boutté Y,Jonsson K,McFarlane HE,Johnson E,Gendre D,Swarup R,Friml J,Samuels L,Robert S,Bhalerao RP

    更新日期:2013-10-01 00:00:00

  • Vibrio cholerae type 6 secretion system effector trafficking in target bacterial cells.

    abstract::The type 6 secretion system (T6SS) is used by many Gram-negative bacterial species to deliver toxic effector proteins into nearby bacteria prey cells to kill or inhibit their growth. VgrG proteins are core conserved secretion substrates of the T6SS and one subset of T6SS effectors consists of VgrG proteins with C-term...

    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.1711219114

    authors: Ho BT,Fu Y,Dong TG,Mekalanos JJ

    更新日期:2017-08-29 00:00:00

  • Drosophila IRBP bZIP heterodimer binds P-element DNA and affects hybrid dysgenesis.

    abstract::In Drosophila, P-element transposition causes mutagenesis and genome instability during hybrid dysgenesis. The P-element 31-bp terminal inverted repeats (TIRs) contain sequences essential for transposase cleavage and have been implicated in DNA repair via protein-DNA interactions with cellular proteins. The identity 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.1613508113

    authors: Francis MJ,Roche S,Cho MJ,Beall E,Min B,Panganiban RP,Rio DC

    更新日期:2016-11-15 00:00:00

  • Permanent and panerythroid correction of murine beta thalassemia by multiple lentiviral integration in hematopoietic stem cells.

    abstract::Achieving long-term pancellular expression of a transferred gene at therapeutic level in a given hematopoietic lineage remains an important goal of gene therapy. Advances have recently been made in the genetic correction of the hemoglobinopathies by means of lentiviral vectors and large locus control region (LCR) deri...

    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.212507099

    authors: Imren S,Payen E,Westerman KA,Pawliuk R,Fabry ME,Eaves CJ,Cavilla B,Wadsworth LD,Beuzard Y,Bouhassira EE,Russell R,London IM,Nagel RL,Leboulch P,Humphries RK

    更新日期:2002-10-29 00:00:00

  • On the law of the iterated logarithm.

    abstract::The law of the iterated logarithm provides a family of bounds all of the same order such that with probability one only finitely many partial sums of a sequence of independent and identically distributed random variables exceed some members of the family, while for others infinitely many do so. In the former case, the...

    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.63.2.289

    authors: Slivka J

    更新日期:1969-06-01 00:00:00

  • Benefit of pulsation in soft corals.

    abstract::Soft corals of the family Xeniidae exhibit a unique, rhythmic pulsation of their tentacles (Movie S1), first noted by Lamarck nearly 200 y ago. However, the adaptive benefit of this perpetual, energetically costly motion is poorly understood. Using in situ underwater particle image velocimetry, we found that the pulsa...

    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.1301826110

    authors: Kremien M,Shavit U,Mass T,Genin A

    更新日期:2013-05-28 00:00:00

  • Freezing immunoglobulins to see them move.

    abstract::The issue of protein dynamics and its implications in the biological function of proteins are arousing greater and greater interest in different fields of molecular biology. In cryo-electron tomography experiments one may take several snapshots of a given biological macromolecule. In principle, a large enough collecti...

    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.0400119101

    authors: Bongini L,Fanelli D,Piazza F,De Los Rios P,Sandin S,Skoglund U

    更新日期:2004-04-27 00:00:00

  • Efficient detection and post-surgical monitoring of colon cancer with a multi-marker DNA methylation liquid biopsy.

    abstract::Multiplex assays, involving the simultaneous use of multiple circulating tumor DNA (ctDNA) markers, can improve the performance of liquid biopsies so that they are highly predictive of cancer recurrence. We have developed a single-tube methylation-specific quantitative PCR assay (mqMSP) that uses 10 different methylat...

    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.2017421118

    authors: Jin S,Zhu D,Shao F,Chen S,Guo Y,Li K,Wang Y,Ding R,Gao L,Ma W,Lu T,Li D,Zhang Z,Cai S,Liang X,Song H,Ji L,Li J,Zheng Z,Jiang F,Wu X,Luan J,Zhang H,Yang Z,Cantor CR,Xu C,Ding C

    更新日期:2021-02-02 00:00:00

  • Triplet states in photosystem I of spinach chloroplasts and subchloroplast particles.

    abstract::We report light-induced electron paramagnetic resonance triplet spectra from samples of chloroplasts or digitonin photosystem I particles that depend upon the dark redox state of the bound acceptors of photosystem I. If the reaction centers are prepared in the redox state P-700 A X- FdB-FdA-, then upon illumination at...

    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.76.10.5124

    authors: Frank HA,McLean MB,Sauer K

    更新日期:1979-10-01 00:00:00

  • Electron-nuclear double resonance of the hydrogen peroxide compound of cytochrome c peroxidase: identification of the free radical site with a methionyl cluster.

    abstract::The results of electron-nuclear double resonance and electron paramagnetic resonance (EPR) studies on the hydrogen peroxide compound of yeast cytochrome c peroxidase are inconsistent with previous proposals for the source of the EPR signal in this compound, in particular with its identification with an aromatic amino ...

    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.76.12.6132

    authors: Hoffman BM,Roberts JE,Brown TG,Kang CH,Margoliash E

    更新日期:1979-12-01 00:00:00

  • Aberrant calcium signaling by transglutaminase-mediated posttranslational modification of inositol 1,4,5-trisphosphate receptors.

    abstract::The inositol 1,4,5-trisphosphate receptor (IP3R) in the endoplasmic reticulum mediates calcium signaling that impinges on intracellular processes. IP3Rs are allosteric proteins comprising four subunits that form an ion channel activated by binding of IP3 at a distance. Defective allostery in IP3R is considered crucial...

    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.1409730111

    authors: Hamada K,Terauchi A,Nakamura K,Higo T,Nukina N,Matsumoto N,Hisatsune C,Nakamura T,Mikoshiba K

    更新日期:2014-09-23 00:00:00