当前位置： SCI文献检索 > ACS Chemical Biology期刊下所有文献 > A Versatile Transcription-Translation in One Approach for Activation of Cryptic Biosynthetic Gene Clusters.

A Versatile Transcription-Translation in One Approach for Activation of Cryptic Biosynthetic Gene Clusters.

Abstract：

:The ever-growing drug resistance problem worldwide highlights the urgency to discover and develop new drugs. Microbial natural products are a prolific source of drugs. Genome sequencing has revealed a tremendous amount of uncharacterized natural product biosynthetic gene clusters (BGCs) encoded within microbial genomes, most of which are cryptic or express at very low levels under standard culture conditions. Therefore, developing effective strategies to awaken these cryptic BGCs is of great interest for natural product discovery. In this study, we designed and validated a Transcription-Translation in One (TTO) approach for activation of cryptic BGCs. This approach aims to alter the metabolite profiles of target strains by directly overexpressing exogenous rpsL (encoding ribosomal protein S12) and rpoB (encoding RNA polymerase β subunit) genes containing beneficial mutations for natural product production using a plug-and-play plasmid system. As a result, this approach bypasses the tedious screening work and overcomes the false positive problem in the traditional ribosome engineering approach. In this work, the TTO approach was successfully applied to activating cryptic BGCs in three Streptomyces strains, leading to the discovery of two aromatic polyketide antibiotics, piloquinone and homopiloquinone. We further identified a single BGC responsible for the biosynthesis of both piloquinone and homopiloquinone, which features an unusual starter unit incorporation step. This powerful strategy can be further exploited for BGC activation in strains even beyond streptomycetes, thus facilitating natural product discovery research in the future.

journal_name

ACS Chem Biol

journal_title

ACS chemical biology

authors

Zhang Q,Ren JW,Wang W,Zhai J,Yang J,Liu N,Huang Y,Chen Y,Pan G,Fan K

doi

10.1021/acschembio.0c00581

subject

Has Abstract

pub_date

2020-09-18 00:00:00

pages

2551-2557

issue

9

eissn

1554-8929

issn

1554-8937

journal_volume

15

pub_type

杂志文章

相关文献

ACS Chemical Biology文献大全
  • Molecular tweezers inhibit islet amyloid polypeptide assembly and toxicity by a new mechanism.

    abstract：:In type-2 diabetes (T2D), islet amyloid polypeptide (IAPP) self-associates into toxic assemblies causing islet β-cell death. Therefore, preventing IAPP toxicity is a promising therapeutic strategy for T2D. The molecular tweezer CLR01 is a supramolecular tool for selective complexation of K residues in (poly)peptides. ...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.5b00146

    authors： Lopes DH,Attar A,Nair G,Hayden EY,Du Z,McDaniel K,Dutt S,Bravo-Rodriguez K,Mittal S,Klärner FG,Wang C,Sanchez-Garcia E,Schrader T,Bitan G

    更新日期：2015-06-19 00:00:00

  • Chemical Tools for Selective Activity Profiling of Endogenously Expressed MMP-14 in Multicellular Models.

    abstract：:Matrix metalloproteases (MMPs) are a large family of zinc-dependent endopeptidases involved in a diverse set of physiological and pathological processes, most notably in cancer. Current methods for imaging and quantifying MMP activity lack sufficient selectivity and spatiotemporal resolution to allow studies of specif...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.8b00562

    authors： Amara N,Tholen M,Bogyo M

    更新日期：2018-09-21 00:00:00

  • Fragment Assembly Approach Based on Graph/Network Theory with Quantum Chemistry Verifications for Assigning Multidimensional NMR Signals in Metabolite Mixtures.

    abstract：:The abundant observation of chemical fragment information for molecular complexities is a major advantage of biological NMR analysis. Thus, the development of a novel technique for NMR signal assignment and metabolite identification may offer new possibilities for exploring molecular complexities. We propose a new sig...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.5b00894

    authors： Ito K,Tsutsumi Y,Date Y,Kikuchi J

    更新日期：2016-04-15 00:00:00

  • Crystal Structures of Fumarate Hydratases from Leishmania major in a Complex with Inhibitor 2-Thiomalate.

    abstract：:Leishmaniases affect the poorest people on earth and have no effective drug therapy. Here, we present the crystal structure of the mitochondrial isoform of class I fumarate hydratase (FH) from Leishmania major and compare it to the previously determined cytosolic Leishmania major isoform. We further describe the mecha...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.8b00972

    authors： Feliciano PR,Drennan CL,Nonato MC

    更新日期：2019-02-15 00:00:00

  • Profiling heparin-chemokine interactions using synthetic tools.

    abstract：:Glycosaminoglycans (GAGs), such as heparin or heparan sulfate, are required for the in vivo function of chemokines. Chemokines play a crucial role in the recruitment of leukocyte subsets to sites of inflammation and lymphocytes trafficking. GAG-chemokine interactions mediate cell migration and determine which leukocyt...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb700159m

    authors： de Paz JL,Moseman EA,Noti C,Polito L,von Andrian UH,Seeberger PH

    更新日期：2007-11-20 00:00:00

  • Engineered EGF-A Peptides with Improved Affinity for Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9).

    abstract：:The epidermal growth-factor-like domain A (EGF-A) of the low-density lipoprotein (LDL) receptor is a promising lead for therapeutic inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9). However, the clinical potential of EGF-A is limited by its suboptimal affinity for PCSK9. Here, we use phage display t...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.0c00991

    authors： Tombling BJ,Lammi C,Lawrence N,Li J,Arnoldi A,Craik DJ,Wang CK

    更新日期：2021-01-29 00:00:00

  • Allostery, Recognition of Nascent Peptidoglycan, and Cross-linking of the Cell Wall by the Essential Penicillin-Binding Protein 2x of Streptococcus pneumoniae.

    abstract：:Transpeptidases, members of the penicillin-binding protein (PBP) families, catalyze cross-linking of the bacterial cell wall. This transformation is critical for the survival of bacteria, and it is the target of inhibition by β-lactam antibiotics. We report herein our structural insights into catalysis by the essentia...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.7b00817

    authors： Bernardo-García N,Mahasenan KV,Batuecas MT,Lee M,Hesek D,Petráčková D,Doubravová L,Branny P,Mobashery S,Hermoso JA

    更新日期：2018-03-16 00:00:00

  • The Hidden Conformation of Lewis x, a Human Histo-Blood Group Antigen, Is a Determinant for Recognition by Pathogen Lectins.

    abstract：:Histo-blood group epitopes are fucosylated branched oligosaccharides with well-defined conformations in solution that are recognized by receptors, such as lectins from pathogens. We report here the results of a series of experimental and computational endeavors revealing the unusual distortion of histo-blood group ant...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.6b00333

    authors： Topin J,Lelimousin M,Arnaud J,Audfray A,Pérez S,Varrot A,Imberty A

    更新日期：2016-07-15 00:00:00

  • Specific Triacylglycerols Accumulate via Increased Lipogenesis During 5-FU-Induced Apoptosis.

    abstract：:Lipids are emerging as key regulators of fundamental cellular processes including cell survival, division, and death. Apoptosis, a form of programmed cell death, is accompanied by numerous membrane-related phenotypic changes. However, we have an incomplete understanding of the involvement of specific lipid structures ...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.6b00410

    authors： Li N,Lizardo DY,Atilla-Gokcumen GE

    更新日期：2016-09-16 00:00:00

  • Chromophore-assisted light inactivation of HaloTag fusion proteins labeled with eosin in living cells.

    abstract：:Chromophore-assisted light inactivation (CALI) is a potentially powerful tool for the acute disruption of a target protein inside living cells with high spatiotemporal resolution. This technology, however, has not been widely utilized, mainly because of the lack of an efficient chromophore as the photosensitizing agen...

    journal_title：ACS chemical biology

    pub_type： 信件

    doi：10.1021/cb100431e

    authors： Takemoto K,Matsuda T,McDougall M,Klaubert DH,Hasegawa A,Los GV,Wood KV,Miyawaki A,Nagai T

    更新日期：2011-05-20 00:00:00

  • Botryllamides: natural product inhibitors of ABCG2.

    abstract：:ABCG2 is a membrane-localized, human transporter protein that has been demonstrated to reduce the intracellular accumulation of substrates through ATP-dependent efflux. Highly expressed in placental syncytiotrophoblasts, brain microvasculature, and the gastrointestinal tract, ABCG2 has been shown to mediate normal tis...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb900134c

    authors： Henrich CJ,Robey RW,Takada K,Bokesch HR,Bates SE,Shukla S,Ambudkar SV,McMahon JB,Gustafson KR

    更新日期：2009-08-21 00:00:00

  • Linking High-Throughput Screens to Identify MoAs and Novel Inhibitors of Mycobacterium tuberculosis Dihydrofolate Reductase.

    abstract：:Though phenotypic and target-based high-throughput screening approaches have been employed to discover new antibiotics, the identification of promising therapeutic candidates remains challenging. Each approach provides different information, and understanding their results can provide hypotheses for a mechanism of act...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.7b00468

    authors： Santa Maria JP Jr,Park Y,Yang L,Murgolo N,Altman MD,Zuck P,Adam G,Chamberlin C,Saradjian P,Dandliker P,Boshoff HIM,Barry CE 3rd,Garlisi C,Olsen DB,Young K,Glick M,Nickbarg E,Kutchukian PS

    更新日期：2017-09-15 00:00:00

  • Cell-Penetrating Peptides Escape the Endosome by Inducing Vesicle Budding and Collapse.

    abstract：:Cell-penetrating peptides (CPPs) are capable of delivering membrane-impermeable cargoes (including small molecules, peptides, proteins, nucleic acids, and nanoparticles) into the cytosol of mammalian cells and have the potential to revolutionize biomedical research and drug discovery. However, the mechanism of action ...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.0c00478

    authors： Sahni A,Qian Z,Pei D

    更新日期：2020-09-18 00:00:00

  • A hexylchloride-based catch-and-release system for chemical proteomic applications.

    abstract：:Bioorthogonal ligation methods that allow the selective conjugation of fluorophores or biotin to proteins and small molecule probes that contain inert chemical handles are an important component of many chemical proteomic strategies. Here, we present a new catch-and-release enrichment strategy that utilizes a hexylchl...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb300623a

    authors： Brigham JL,Perera BG,Maly DJ

    更新日期：2013-04-19 00:00:00

  • Sensing proteins through nanopores: fundamental to applications.

    abstract：:Proteins subjected to an electric field and forced to pass through a nanopore induce blockades of ionic current that depend on the protein and nanopore characteristics and interactions between them. Recent advances in the analysis of these blockades have highlighted a variety of phenomena that can be used to study pro...

    journal_title：ACS chemical biology

    pub_type： 杂志文章,评审

    doi：10.1021/cb300449t

    authors： Oukhaled A,Bacri L,Pastoriza-Gallego M,Betton JM,Pelta J

    更新日期：2012-12-21 00:00:00

  • Unleashing biocatalysis/chemical catalysis synergies for efficient biomass conversion.

    abstract：:The goal of incorporating renewable carbon into the fuel and chemical enterprise will most likely be successful when combined systems of biocatalysts and chemical catalysts are exploited. Significant efforts in the biocatalytic release of sugars from biomass are being pursued for subsequent use in fermentation. Two re...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb7001522

    authors： Shanks BH

    更新日期：2007-08-17 00:00:00

  • Chemical Probe To Monitor the Parkinsonism-Associated Protein DJ-1 in Live Cells.

    abstract：:Reactive oxygen species (ROS) play an important role in the onset of Parkinson's disease (PD), and deciphering protective mechanisms is a major goal for therapeutic development. Here, DJ-1 (PARK7) gained major attention when a conserved cysteine residue with a putative role in oxidative stress sensing/protection was l...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.8b00633

    authors： Drechsel J,Mandl FA,Sieber SA

    更新日期：2018-08-17 00:00:00

  • Recruitment and Regulation of the Non-ribosomal Peptide Synthetase Modifying Cytochrome P450 Involved in Nikkomycin Biosynthesis.

    abstract：:The β-hydroxylation of l-histidine is the first step in the biosynthesis of the imidazolone base of the antifungal drug nikkomycin. The cytochrome P450 (NikQ) hydroxylates the amino acid while it is appended via a phosphopantetheine linker to the non-ribosomal peptide synthetase (NRPS) NikP1. The latter enzyme is comp...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.7b00081

    authors： Wise CE,Makris TM

    更新日期：2017-05-19 00:00:00

  • Cross-Linking Furan-Modified Kisspeptin-10 to the KISS Receptor.

    abstract：:Chemical cross-linking is well-established for investigating protein-protein interactions. Traditionally, photo cross-linking is used but is associated with problems of selectivity and UV toxicity in a biological context. We here describe, with live cells and under normal growth conditions, selective cross-linking of ...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.7b00396

    authors： Vannecke W,Ampe C,Van Troys M,Beltramo M,Madder A

    更新日期：2017-08-18 00:00:00

  • Lipid nanoparticles improve activity of single-stranded siRNA and gapmer antisense oligonucleotides in animals.

    abstract：:We evaluated the abilities of an antisense oligonucleotide (ASO), a small interfering RNA (siRNA), and a single-stranded siRNA (ss-siRNA) to inhibit expression from the PTEN gene in mice when formulated identically with lipid nanoparticles (LNPs). Significantly greater reductions in levels of PTEN mRNA were observed f...

    journal_title：ACS chemical biology

    pub_type： 信件

    doi：10.1021/cb4001316

    authors： Prakash TP,Lima WF,Murray HM,Elbashir S,Cantley W,Foster D,Jayaraman M,Chappell AE,Manoharan M,Swayze EE,Crooke ST

    更新日期：2013-07-19 00:00:00

  • Small Molecule Inhibitors of Human DNA Polymerase λ.

    abstract：:To discover chemical probes to further under-stand the function of individual DNA polymerases, we established a generally applicable high-throughput screening. By applying this technique we discovered three novel inhibitor classes of human DNA polymerase λ (DNA Pol λ), a key enzyme to maintain the genetic integrity of...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb100382m

    authors： Strittmatter T,Bareth B,Immel TA,Huhn T,Mayer TU,Marx A

    更新日期：2011-04-15 00:00:00

  • CB-6644 Is a Selective Inhibitor of the RUVBL1/2 Complex with Anticancer Activity.

    abstract：:RUVBL1 and RUVBL2 are ATPases associated with diverse cellular activities (AAAs) that form a complex involved in a variety of cellular processes, including chromatin remodeling and regulation of gene expression. RUVBLs have a strong link to oncogenesis, where overexpression is correlated with tumor growth and poor pro...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.8b00904

    authors： Assimon VA,Tang Y,Vargas JD,Lee GJ,Wu ZY,Lou K,Yao B,Menon MK,Pios A,Perez KC,Madriaga A,Buchowiecki PK,Rolfe M,Shawver L,Jiao X,Le Moigne R,Zhou HJ,Anderson DJ

    更新日期：2019-02-15 00:00:00

  • Antagonism of c-IAP and XIAP proteins is required for efficient induction of cell death by small-molecule IAP antagonists.

    abstract：:The inhibitor of apoptosis (IAP) proteins are critical regulators of cancer cell survival, which makes them attractive targets for therapeutic intervention in cancers. Herein, we describe the structure-based design of IAP antagonists with high affinities and selectivity (>2000-fold) for c-IAP1 over XIAP and their func...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb900083m

    authors： Ndubaku C,Varfolomeev E,Wang L,Zobel K,Lau K,Elliott LO,Maurer B,Fedorova AV,Dynek JN,Koehler M,Hymowitz SG,Tsui V,Deshayes K,Fairbrother WJ,Flygare JA,Vucic D

    更新日期：2009-07-17 00:00:00

  • Stable RAGE-heparan sulfate complexes are essential for signal transduction.

    abstract：:RAGE (Receptor for Advanced Glycation End-Products) has emerged as a major receptor that mediates vascular inflammation. Signaling through RAGE by damage-associated molecular pattern molecules often leads to uncontrolled inflammation that exacerbates the impact of the underlying disease. Oligomerization of RAGE is bel...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb4001553

    authors： Xu D,Young JH,Krahn JM,Song D,Corbett KD,Chazin WJ,Pedersen LC,Esko JD

    更新日期：2013-07-19 00:00:00

  • Enzymatic Plasticity Inspired by the Diterpene Cyclase CotB2.

    abstract：:Enzymatic plasticity, as a modern term referring to the functional conversion of an enzyme, is significant for enzymatic activity redesign. The bacterial diterpene cyclase CotB2 is a typical plastic enzyme by which its native form precisely conducts a chemical reaction while its mutants diversify the catalytic functio...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.0c00645

    authors： Tang X,Zhang F,Zeng T,Li W,Yin S,Wu R

    更新日期：2020-10-16 00:00:00

  • Molecular Networking and Whole-Genome Analysis Aid Discovery of an Angucycline That Inactivates mTORC1/C2 and Induces Programmed Cell Death.

    abstract：:Rediscovery of known compounds and time consumed in identification, especially high molecular weight compounds with complex structure, have let down interest in drug discovery. In this study, whole-genome analysis of microbe and Global Natural Products Social (GNPS) molecular networking helped in initial understanding...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.0c00026

    authors： Dan VM,J S V,C J S,Sanawar R,Lekshmi A,Kumar RA,Santhosh Kumar TR,Marelli UK,Dastager SG,Pillai MR

    更新日期：2020-03-20 00:00:00

  • Adversarial Controls for Scientific Machine Learning.

    abstract：:New machine learning methods to analyze raw chemical and biological data are now widely accessible as open-source toolkits. This positions researchers to leverage powerful, predictive models in their own domains. We caution, however, that the application of machine learning to experimental research merits careful cons...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.8b00881

    authors： Chuang KV,Keiser MJ

    更新日期：2018-10-19 00:00:00

  • Impaired transport of nucleotides in a mitochondrial carrier explains severe human genetic diseases.

    abstract：:The mitochondrial ADP/ATP carrier (AAC) is a prominent actor in the energetic regulation of the cell, importing ADP into the mitochondria and exporting ATP toward the cytoplasm. Severe genetic diseases have been ascribed to specific mutations in this membrane protein. How minute, well-localized modifications of the tr...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb300012j

    authors： Ravaud S,Bidon-Chanal A,Blesneac I,Machillot P,Juillan-Binard C,Dehez F,Chipot C,Pebay-Peyroula E

    更新日期：2012-07-20 00:00:00

  • Parietal Structures of Escherichia coli Can Impact the D-Cateslytin Antibacterial Activity.

    abstract：:Bacterial resistance to conventional antibiotics is of major concern. Antimicrobial peptides (AMPs) are considered excellent alternatives. Among them, D-cateslytin (D-Ctl, derivative of a host defense peptide) has shown high efficiency against a broad spectrum of bacteria. The first target of AMPs is the outer membran...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/acschembio.0c00622

    authors： Quilès F,Barth D,Peric O,Fantner GE,Francius G

    更新日期：2020-10-16 00:00:00

  • Engineering the polyproline II propensity of a class II major histocompatibility complex ligand peptide.

    abstract：:Our immune system constantly samples peptides found inside the body as a means to detect foreign pathogens, infected cells, and tumorous cells. T cells, which carry out the critical task of distinguishing self from nonself peptides, can only survey peptides that are presented by the major histocompatibility complex pr...

    journal_title：ACS chemical biology

    pub_type： 杂志文章

    doi：10.1021/cb400594q

    authors： Unudurthi SD,Hotta K,Kim CY

    更新日期：2013-11-15 00:00:00