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PolyketidesPolyketide SynthasesStreptomycesGlutamate SynthaseSaccharopolysporaMacrolidesMultienzyme ComplexesAcyl Carrier ProteinAnthraquinonesMultigene FamilyBiosynthetic PathwaysGlutamate-Ammonia LigaseNitric Oxide SynthasePeptide SynthasesArginineNitritesNaphthacenesGibberellaMolecular Sequence DataAcyltransferasesMolecular StructurePyronesNitric OxideCyclizationomega-N-MethylarginineMalonyl Coenzyme AZearalenoneActinobacteriaLactonesEnediynesBryozoaStreptomyces coelicolorPolyenesAmino Acid SequenceOxytetracyclineAcyl Coenzyme ANitric Oxide Synthase Type IIIGenes, BacterialBiological ProductsNaphtholsTransferases (Other Substituted Phosphate Groups)Cyclic GMPGenetic EngineeringSubstrate SpecificityCloning, MolecularBacterial ProteinsStigmatella aurantiacaErythromycinMyxococcalesSequence Analysis, DNAThiolester HydrolasesPeptide Biosynthesis, Nucleic Acid-IndependentStereoisomerismNaphthoquinonesChaetomiumBase SequenceEnzyme InhibitorsNitric Oxide Synthase Type IIProtein Structure, TertiaryPlakortisAlternariaPhylogenyFatty Acid SynthasesAcyl-Carrier Protein S-MalonyltransferaseProtein EngineeringSequence Homology, Amino AcidEndothelium, VascularCells, CulturedChromatography, High Pressure LiquidAnti-Bacterial AgentsEscherichia coliCitrate (si)-SynthaseRheumSequence AlignmentResorcinolsSpiramycinAspergillusPeperomiaAspergillus nidulansRats, Sprague-DawleyPhloroglucinolNatamycin3-Oxoacyl-(Acyl-Carrier-Protein) SynthaseCatalytic DomainSpiro CompoundsActinomycetalesStreptomyces griseusPantetheineHuperziaPeryleneCrystallography, X-RayModels, MolecularBiocatalysisGlycogen SynthasePigments, BiologicalOpen Reading FramesDNA, BacterialAloeRecombinant ProteinsCitrinin
BiosynthesisModular polyketidePKSsBiochemical pathwaysStreptomycesBiosynthetic geneEnzymesAspergillusGenesSecondaryCharacterizationFungiPlasmidMicrobialTypeGroupNaturalLargeModulesProductionDomainWorkPlantsStudyAromaticPolycyclicBiosynthesisPeptidesCondensationSTREPTOMYCESIterativeNonribosomalMetabolicStructurallyTerpenoidsEnzymeSubstrateFattyBioactive moleculesEnzymaticIntermediateFunctionalSynthesisCompoundsBiologicalChainProductsFormationRevealsGroups
Biosynthesis6
  • The biosyntheses of polyketides share striking similarities with fatty acid biosynthesis. (wikipedia.org)
  • The latter contains a conserved Ser residue, post-translationally modified with a phosphopantetheine at the end of which the polyketide chain is covalently bound during biosynthesis as a thioester. (wikipedia.org)
  • 2015. "Divergent mechanistic routes for the formation of gem-dimethyl groups in the biosynthesis of complex polyketides. (lbl.gov)
  • A LAL regulator RimR2 was identified as a positive specific-pathway regulator of rimocidin biosynthesis in M527. (biomedcentral.com)
  • The mupirocin trans-AT polyketide synthase pathway, provides a model system for manipulation of antibiotic biosynthesis. (birmingham.ac.uk)
  • A pathway for stilbene biosynthesis was constructed in Escherichia coli with 4-coumaroyl CoA ligase 1 4CL1) from Arabidopsis thaliana and stilbene synthase (STS) cloned from Arachis hypogaea . (biomedcentral.com)
Modular polyketide1
  • Probing the flexibility of an iterative modular polyketide synthase with non-native substrates in vitro. (lbl.gov)
PKSs4
  • Polyketide synthases (PKSs) are a family of multi-domain enzymes or enzyme complexes that produce polyketides, a large class of secondary metabolites, in bacteria, fungi, plants, and a few animal lineages. (wikipedia.org)
  • This type of type I PKSs is also referred to as cis-acyltransferase polyketide synthases (cis-AT PKSs). (wikipedia.org)
  • NR-PKSs - non-reducing PKSs, the products of which are true polyketides PR-PKSs - partially reducing PKSs FR-PKSs - fully reducing PKSs, the products of which are fatty acid derivatives Each type I polyketide-synthase module consists of several domains with defined functions, separated by short spacer regions. (wikipedia.org)
  • Multienzyme polyketide synthases (PKSs) and non-ribosomal peptide synthetases (NRPSs) are molecular assembly lines that biosynthesize complex natural products, making them ideal for rational enzyme engineering. (lbl.gov)
Biochemical pathways2
  • With the aim of producing important chemicals in microorganisms, we focus our efforts at investigating novel biochemical pathways and engineering microorganisms to host these pathways. (lbl.gov)
  • The rich chemical and structural diversity of natural products make them attractive sources for biochemical pathways that can lead to novel chemicals. (lbl.gov)
Streptomyces1
  • Firstly, a three-gene cluster coding for a cyclodipeptide synthase, a prenyltransferase, and a methyltransferase was identified in Streptomyces aurantiacus by genome mining. (uni-marburg.de)
Biosynthetic gene1
  • The cloning and characterization of a major portion of the herbimycin (hbm) biosynthetic gene cluster containing the polyketide synthase (PKS) genes and some other genes involved in post-PKS modifications are described. (readabstracts.com)
Enzymes4
  • Our work in biochemistry and microbiology focuses on understanding unknown metabolic pathways, enzymes or microbial processes that will be central to be able to engineer new metabolic functions inside cells. (lbl.gov)
  • When we are faced with unknown pathway enzymes, the Keasling Lab uses a variety of genomics tools and enzyme assays to discover the missing biosynthetic steps. (lbl.gov)
  • This includes the mapping of biosynthetic pathways, characterization of involved enzymes, as well as the genetic basis and the evolutionary forces that shape these systems. (dtu.dk)
  • The majority of our projects focus on biosynthetic pathways that include enzymes belonging to the polyketide synthase (PKS) class. (dtu.dk)
Aspergillus1
Genes2
  • The PKS genes for a certain polyketide are usually organized in one operon or in gene clusters. (wikipedia.org)
  • SMs are biosynthesized from primary metabolites in specialized pathways (i.e. polyketides or mevalonate pathways derived from Acetyl Coenzyme A, or amino acids) and some genes are clustered together. (123dok.org)
Secondary1
  • In fungal secondary metabolite systems, we are especially interested in the role of horizontal gene transfer events, the organization of biosynthetic pathways, self-resistance mechanisms and how gene clusters are formed, expand and erode. (dtu.dk)
Characterization1
  • 2012. "Functional characterization of four sesquiterpene synthases from Ricinus communis (Caster Bean). (lbl.gov)
Fungi2
  • This work is based on our extensive experience with natural biosynthetic pathways, especially polyketide synthases (type I-III), from fungi, insects, bacteria, and plants. (dtu.dk)
  • in filamentous fungi, the his-asp phosphorelay signaling system and hog pathway are involved in the action of the fungicides, fludioxonil, and iprodione, as well as osmotic and oxidative stress responses. (liverpool.ac.uk)
Plasmid1
  • A plasmid expressing mupLMNOPVCFU+macpE together with a derivative of the producer P. fluorescens strain NCIMB10586 lacking the mup cluster allowed conversion of PA-B to PA-A . MupN converts apo-mAcpE to holo-form while MupM is a mupirocin-resistant isoleucyl tRNA synthase, preventing self-poisoning. (birmingham.ac.uk)
Microbial1
  • It is our vision to create a series of programmable microbial platforms that allows for the synthesis of any biological relevant carbon skeleton, thereby bypassing the time-consuming task of identifying natural pathways. (dtu.dk)
Type2
  • The minimal composition of a type I PKS module consists of an acyltransferase (AT) domain, which is responsible for choosing the building block to be used, a keto synthase (KS) domain, which catalyzes the C-C bond formation and an acyl carrier protein (ACP) domain, also known as thiolation domain. (wikipedia.org)
  • A type III polyketide synthase then sequentially adds three acetate extender units, derived from malonyl-CoA, to a single activated 4-coumaroyl-CoA starter unit. (biomedcentral.com)
Group2
  • The Biosynthetic Pathway Engineering research group is committed to further our understanding of biosynthetic pathways, and to utilize this knowledge to implement natural biosynthetic pathways and for the design of artificial (synthetic) pathways for the production of small molecules. (dtu.dk)
  • This study provides an enzyme with a high substrate promiscuity from the less explored prenyltransferase group in cyclodipeptide synthase-related pathways. (uni-marburg.de)
Natural3
  • The biosynthetic pathways for some of the most important natural products from plants are not known. (lbl.gov)
  • The applied research aims at developing general strategies/tools for implementing and designing synthetic pathways for the production of natural and new-to-nature compounds. (dtu.dk)
  • Modifications on the core structure by an aryl acid reductase (UttJ), a putative nonheme FeII/2-oxoglutarate dependent oxygenase (UttH), a cytochrome P450 enzyme (UttC) and a O-methyltransferase (UttF) led to the final product ustethylin A. This study is the first report on the biosynthetic pathway of a phenethyl-containing natural product. (uni-marburg.de)
Large1
  • The use of Red/ET recombination to generate a large number of shuttle plasmids from a diverse library of chimeric domains for directed evolution of the pikromycin polyketide synthase (PKS) is reported. (readabstracts.com)
Modules1
  • 2014. "In vitro analysis of carboxyacyl substrate tolerance in the loading and first extension modules of Borrelidin polyketide synthase. (lbl.gov)
Production2
  • 2011. "Structure of a three-domain sesquiterpene synthase: a prospective target for advanced biofuels production. (lbl.gov)
  • Depending on the polyketide synthase activity, chalcone synthase (CHS, EC 2.3.1.74) or stilbene synthase (STS, EC 2.3.1.95), subsequent folding and cyclization of the generated tetraketide intermediate results either in the production of a chalcone or stilbene ring structure. (biomedcentral.com)
Domain1
  • Gene deletion and heterologous expression proved that the phenethyl core structure is assembled by a polyketide synthase (UttA) harboring a methyltransferase domain. (uni-marburg.de)
Work1
Plants2
  • Examples include the discovery of the cytochrome P450 responsible for oxidizing amorphadiene to artemisinic acid in Artemisia annua and terpene synthases responsible for producing a variety of terpenoids in plants and microorganisms. (lbl.gov)
  • 2010. "Cloning of casbene and neocembrene synthases from Euphorbiaceae plants and expression in Saccharomyces cerevisiae . (lbl.gov)
Study1
Aromatic7
  • New insights into the formation of fungal aromatic polyketides. (nih.gov)
  • Fungal aromatic polyketides constitute a large family of bioactive natural products and are synthesized by the non-reducing group of iterative polyketide synthases (PKSs). (nih.gov)
  • This Review highlights recent insights into these questions, with a particular focus on the biosynthetic programming of fungal aromatic polyketides, and draws comparisons with the allied biosynthetic processes in bacteria. (nih.gov)
  • Polycyclic aromatic polyketides with tricyclic benzoisochrome quinone skeletons. (nih.gov)
  • HN - 2024 FX - Neovascularization, Pathologic FX - Neovascularization, Physiologic MH - Angucyclines and Angucyclinones UI - D000095602 MN - D2.455.426.559.847.149.401 MN - D2.540.576.375 MN - D2.806.250.45 MN - D4.345.674.313 MN - D4.615.149.401 MS - Polycyclic aromatic polyketides with tetracyclic angular benz(a)anthracene skeletons. (nih.gov)
  • 13. Cloning, sequencing and analysis of the enterocin biosynthesis gene cluster from the marine isolate 'Streptomyces maritimus': evidence for the derailment of an aromatic polyketide synthase. (nih.gov)
  • While type II polyketide synthase pathways typically produce polycyclic aromatic items just like the antibiotic tetracycline as well as the SCH 54292 anticancer agent doxorubicin10 aromatic polyketides known as wailupemycins are produced only as minimal items from the enterocin biosynthetic pathway7. (cell-metabolism.com)
Polycyclic1
  • Alchivemycin A (AVM, 1 ) is a potent antibacterial polycyclic polyketide with an unprecedented skeleton originally isolated from a plant-derived actinomycete Streptomyces sp. (springernature.com)
Biosynthesis12
  • Bacterial trans -acyltransferase polyketide synthases ( trans -AT PKSs) are among the most complex known enzymes from secondary metabolism and are responsible for the biosynthesis of highly diverse bioactive polyketides. (nature.com)
  • Helfrich, E. J. & Piel, J. Biosynthesis of polyketides by trans -AT polyketide synthases. (nature.com)
  • The biosyntheses of polyketides share striking similarities with fatty acid biosynthesis. (wikipedia.org)
  • The latter contains a conserved Ser residue, post-translationally modified with a phosphopantetheine at the end of which the polyketide chain is covalently bound during biosynthesis as a thioester. (wikipedia.org)
  • The biosynthesis of various types of natural products such as polyketides, non-ribosomal peptides and terpenoids is based on the core enzymes polyketide synthase (PKS), non-ribosomal peptide synthase (NRPS), and terpene synthase (TS). (springernature.com)
  • The thioesterase (TE)-mediated macrocyclization is regarded as the most canonical strategy in polyketide and nonribosomal peptide biosynthesis, where a hydroxyl or an amino group in the polyketide or peptide acyl chain acts as an internal nucleophile to attack the TE-tethered carbonyl carbon, generating a macrolactone or a macrolactam. (springernature.com)
  • a dual functional enzyme, LkcE, catalyzes a unique amide oxidation and a subsequent Mannich reaction to form the polyketide macrocycle in the lankacidin biosynthesis. (springernature.com)
  • 6. Oxazolomycin biosynthesis in Streptomyces albus JA3453 featuring an "acyltransferase-less" type I polyketide synthase that incorporates two distinct extender units. (nih.gov)
  • 10. The biosynthetic gene cluster for the anticancer drug bleomycin from Streptomyces verticillus ATCC15003 as a model for hybrid peptide-polyketide natural product biosynthesis. (nih.gov)
  • ascomyceticus (ATCC 14891) contains genes for biosynthesis of unusual polyketide extender units. (nih.gov)
  • 19. Leinamycin biosynthesis revealing unprecedented architectural complexity for a hybrid polyketide synthase and nonribosomal peptide synthetase. (nih.gov)
  • My team has accumulated a good body of work on bioactive natural product discovery (from polyketides and peptides to alkaloids) and their biosynthesis, and new enzyme investigation as shown below. (abdn.ac.uk)
Peptides2
  • isolated from the rhizospheric soil of Panax notoginseng: isolation, antimicrobial activity and biosynthetic potential for polyketides and non-ribosomal peptides. (nih.gov)
  • The discovery we made offers an alternative to rational engineering of pathways to generate bioactive peptides. (abdn.ac.uk)
Condensation4
  • The side chain volume of position 256 influences both the number of condensation reactions during polyketide chain extension and the conformation of the triketide and tetraketide intermediates during the cyclization reaction. (nih.gov)
  • PKS employ short chain fatty acyl CoAs in Claisen condensation reactions to produce polyketides. (lbl.gov)
  • STREPTOMYCES COELICOLOR , using type II minimal polyketide synthase involving condensation of 8 malonyl-CoA in actinorhodin pathway. (nih.gov)
  • STREPTOMYCES, using type II polyketide synthase involving condensation of acetyl CoA and 9 malonyl-CoA. (nih.gov)
STREPTOMYCES3
  • 5. The biosynthetic gene cluster for the antitumor drug bleomycin from Streptomyces verticillus ATCC15003 supporting functional interactions between nonribosomal peptide synthetases and a polyketide synthase. (nih.gov)
  • Here we used electron cryo-microscopy to determine sub-nanometre-resolution three-dimensional reconstructions of a full-length PKS module from the bacterium Streptomyces venezuelae that revealed an unexpectedly different architecture compared to the homologous dimeric mammalian fatty acid synthase. (inra.fr)
  • The architecture of a full-length PKS module from the pikromycin pathway of Streptomyces venezuelae creates a reaction chamber for the intramodule acyl carrier protein (ACP) domain that carries building blocks and intermediates between acyltransferase, ketosynthase and ketoreductase active sites (see accompanying paper). (inra.fr)
Iterative1
  • Based on this strain, the downstream α-farnesene synthesis pathway was overexpressed by iterative integration. (springer.com)
Nonribosomal1
  • AVM is biosynthetically derived from a hybrid cis -AT polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) pathway. (springernature.com)
Metabolic3
  • In this lecture, he examines how engineering metabolic pathways in microorganisms can provide new antibiotics and other bioactive natural products. (rse.org.uk)
  • By metabolic profiling and molecular network analyses of the model organism B. thailandensis we found that the primary products of the cryptic pathway are unusual cyclopropanol-substituted polyketides. (leibniz-hki.de)
  • Recently discovery appearance and biochemical analyses from the enterocin biosynthetic gene cluster including reconstitution from the metabolic pathway confirmed further participation of the sort II polyketide synthase EncABC as well as the NADPH-dependent reductase EncD6 7 9 (Fig. 1). (cell-metabolism.com)
Structurally2
  • We demonstrate the applicative scope in several examples, including the characterization of new variants of bioactive natural products as well as structurally new polyketides from unusual bacterial sources. (nature.com)
  • Chalcone synthase (CHS) belongs to the family of type III polyketide synthases (PKS) that catalyze formation of structurally diverse polyketides. (nih.gov)
Terpenoids1
  • Asides from polyketide, terpenoids are also synthesized using acetyl-CoA as a precursor. (springer.com)
Enzyme3
  • This study reveals for the first time, to our knowledge, the structural basis for both intramodule and intermodule substrate transfer in polyketide synthases, and establishes a new model for molecular dissection of these multifunctional enzyme systems. (inra.fr)
  • The polyketide synthase (PKS) mega-enzyme assembly line uses a modular architecture to synthesize diverse and bioactive natural products that often constitute the core structures or complete chemical entities for many clinically approved therapeutic agents. (inra.fr)
  • To maximize the effect of this pathway, we first tested and selected a phosphoketolase (Xfpk) enzyme with high activity in P. putida . (biomedcentral.com)
Substrate2
  • The ACP domain is differentially and precisely positioned after polyketide chain substrate loading on the active site of the ketosynthase, after extension to the beta-keto intermediate, and after beta-hydroxy product generation. (inra.fr)
  • This function provides new understanding in to the fine-tuning from the flavin cofactor in offsetting the innate reactivity of the polyketide substrate to immediate its effective electrocyclization. (cell-metabolism.com)
Fatty2
  • Unlike fatty acid synthases that use a single module iteratively to produce the nascent chains, PKS are composed of discreet modules, each catalyzing the chain growth of a single step. (lbl.gov)
  • The unexpected module architecture revealed a striking evolutionary divergence of the polyketide synthase compared to its metazoan fatty acid synthase homolog, as well as remarkable conformational rearrangements dependent on its biochemical state during the full catalytic cycle. (inra.fr)
Bioactive molecules2
Enzymatic1
  • End products vary depending on organisms, substrates, and enzymatic pathways. (lookformedical.com)
Intermediate2
  • In contrast, the carrier from the preceding module uses a separate entrance outside the reaction chamber to deliver the upstream polyketide intermediate for subsequent extension and modification. (inra.fr)
  • Many high-value products, such as isoprenoids, butanol, and polyketides, are derived from the intermediate acetyl-CoA, a key compound connecting the glycolysis and the tricarboxylic acid (TCA) cycle [ 10 ]. (biomedcentral.com)
Functional1
  • The first 3D structures of a full polyketide synthase module in different functional states were obtained recently by electron cryo-microscopy. (inra.fr)
Synthesis1
  • Other classifications include the degree of reduction performed during the synthesis of the growing polyketide chain. (wikipedia.org)
Compounds3
  • The majority of dinoflagellate toxins adversely affecting human health are polyketides, natural organic compounds consisting of long carbon chains with oxygen-containing rings and synthesized by complex proteins known as polyketide synthases (PKS). (noaa.gov)
  • Some natural polyketide producers yield 80 or more grams per liter of much larger compounds. (lbl.gov)
  • Polyketide natural products constitute a broad class of compounds with diverse structural features and biological activities. (inra.fr)
Biological1
  • Until now, there has not been a biological pathway to isooctane. (lbl.gov)
Chain2
  • Gly256 resides on the surface of the CHS active site that is in direct contact with the polyketide chain derived from malonyl-CoA. (nih.gov)
  • The technology offers similar advantages as producing diacids from the PKS pathway and may be more efficient than PKS pathway for shorter chain diacids. (lbl.gov)
Products1
  • Professor Simpson then outlined the rationale for his approach of looking again at natural products and finding out if molecular genetic manipulations of existing pathways can offer new opportunities for creating novel antibiotics designed to be active and easily produced. (rse.org.uk)
Formation1
  • Our hypothesis is that PKS synthesizes the backbones for brevetoxin (called polyenes) in the chloroplast and then exports them to other cellular compartments for polyketide ring formation. (noaa.gov)
Reveals1
  • TP-A0882 reveals putative butyrolactol biosynthetic pathway. (nih.gov)
Groups1
  • HN - 2024 BX - Amphidinolide BX - Iriomoteolide BX - Iriomoteolides MH - Amphidinols UI - D000095722 MN - D2.355.291.933.63 MN - D2.540.576.625.63 MN - D4.345.241.654.63 MN - D4.345.674.625.63 MN - D23.946.580.80 MS - Long linear polyketides with polyol groups and polyolefins and core motifs of two tetrahydropyran rings produced by marine dinoflagellates such as AMPHIDINIUM. (nih.gov)