polyketide synthases

Summary

Summary: Large enzyme complexes composed of a number of component enzymes that are found in STREPTOMYCES which biosynthesize MACROLIDES and other polyketides.

Top Publications

  1. pmc A singular enzymatic megacomplex from Bacillus subtilis
    Paul D Straight
    Department of Microbiology and Molecular Genetics and Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 104:305-10. 2007
  2. ncbi Polyketide synthases and nonribosomal peptide synthetases: the emerging view from bacterial genomics
    Stefano Donadio
    KtedoGen, via Fantoli 16 15, 20132 Milan, Italy
    Nat Prod Rep 24:1073-109. 2007
  3. pmc SBSPKS: structure based sequence analysis of polyketide synthases
    Swadha Anand
    National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India
    Nucleic Acids Res 38:W487-96. 2010
  4. pmc Intimate bacterial-fungal interaction triggers biosynthesis of archetypal polyketides in Aspergillus nidulans
    Volker Schroeckh
    Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology Hans Knöll Institute, 07745 Jena, Germany
    Proc Natl Acad Sci U S A 106:14558-63. 2009
  5. pmc Antitumor polyketide biosynthesis by an uncultivated bacterial symbiont of the marine sponge Theonella swinhoei
    Jorn Piel
    Department of Bioorganic Chemistry, Max Planck Institute for Chemical Ecology, Hans Knoll Strasse 8, Beutenberg Campus, 07745 Jena, Germany
    Proc Natl Acad Sci U S A 101:16222-7. 2004
  6. ncbi Genomics-driven discovery of PKS-NRPS hybrid metabolites from Aspergillus nidulans
    Sebastian Bergmann
    Leibniz Institute for Natural Product Research and Infection Biology Hans Knöll Institute, Beutenbergstr 11a, 07745 Jena, Germany
    Nat Chem Biol 3:213-7. 2007
  7. pmc Genome sequencing reveals complex secondary metabolome in the marine actinomycete Salinispora tropica
    Daniel W Udwary
    Scripps Institution of Oceanography, University of California at San Diego, La Jolla, CA 92093 0204, USA
    Proc Natl Acad Sci U S A 104:10376-81. 2007
  8. ncbi Phylogenomic and functional domain analysis of polyketide synthases in Fusarium
    Daren W Brown
    Bacterial Foodborne Pathogens and Mycology Research, USDA ARS NCAUR, Peoria, Illinois 61604, USA
    Fungal Biol 116:318-31. 2012
  9. pmc Structure and biosynthesis of heat-stable antifungal factor (HSAF), a broad-spectrum antimycotic with a novel mode of action
    Fengan Yu
    Department of Chemistry, University of Nebraska Lincoln, 729 Hamilton Hall, Lincoln, NE 68588 0304, USA
    Antimicrob Agents Chemother 51:64-72. 2007
  10. ncbi Evolutionary implications of bacterial polyketide synthases
    Holger Jenke-Kodama
    Humboldt University, Institute of Biology, Chausseestrasse, Berlin, Germany
    Mol Biol Evol 22:2027-39. 2005

Detail Information

Publications259 found, 100 shown here

  1. pmc A singular enzymatic megacomplex from Bacillus subtilis
    Paul D Straight
    Department of Microbiology and Molecular Genetics and Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 104:305-10. 2007
    Nonribosomal peptide synthetases (NRPS), polyketide synthases (PKS), and hybrid NRPS/PKS are of particular interest, because they produce numerous therapeutic agents, have great potential for engineering novel compounds, and are the ..
  2. ncbi Polyketide synthases and nonribosomal peptide synthetases: the emerging view from bacterial genomics
    Stefano Donadio
    KtedoGen, via Fantoli 16 15, 20132 Milan, Italy
    Nat Prod Rep 24:1073-109. 2007
    ..223 complete bacterial genomes are analyzed, with 281 citations, for the presence of genes encoding modular polyketide synthases (PKS) and nonribosomal peptide synthetases (NRPS)...
  3. pmc SBSPKS: structure based sequence analysis of polyketide synthases
    Swadha Anand
    National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India
    Nucleic Acids Res 38:W487-96. 2010
    b>Polyketide synthases (PKSs) catalyze biosynthesis of a diverse family of pharmaceutically important secondary metabolites...
  4. pmc Intimate bacterial-fungal interaction triggers biosynthesis of archetypal polyketides in Aspergillus nidulans
    Volker Schroeckh
    Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology Hans Knöll Institute, 07745 Jena, Germany
    Proc Natl Acad Sci U S A 106:14558-63. 2009
    ....
  5. pmc Antitumor polyketide biosynthesis by an uncultivated bacterial symbiont of the marine sponge Theonella swinhoei
    Jorn Piel
    Department of Bioorganic Chemistry, Max Planck Institute for Chemical Ecology, Hans Knoll Strasse 8, Beutenberg Campus, 07745 Jena, Germany
    Proc Natl Acad Sci U S A 101:16222-7. 2004
    ....
  6. ncbi Genomics-driven discovery of PKS-NRPS hybrid metabolites from Aspergillus nidulans
    Sebastian Bergmann
    Leibniz Institute for Natural Product Research and Infection Biology Hans Knöll Institute, Beutenbergstr 11a, 07745 Jena, Germany
    Nat Chem Biol 3:213-7. 2007
    ..Here we report a new strategy for the successful induction of a silent metabolic pathway in the important model organism Aspergillus nidulans, which led to the discovery of novel PKS-NRPS hybrid metabolites...
  7. pmc Genome sequencing reveals complex secondary metabolome in the marine actinomycete Salinispora tropica
    Daniel W Udwary
    Scripps Institution of Oceanography, University of California at San Diego, La Jolla, CA 92093 0204, USA
    Proc Natl Acad Sci U S A 104:10376-81. 2007
    ..This study firmly establishes the genus Salinispora as a rich source of drug-like molecules and importantly reveals the powerful interplay between genomic analysis and traditional natural product isolation studies...
  8. ncbi Phylogenomic and functional domain analysis of polyketide synthases in Fusarium
    Daren W Brown
    Bacterial Foodborne Pathogens and Mycology Research, USDA ARS NCAUR, Peoria, Illinois 61604, USA
    Fungal Biol 116:318-31. 2012
    ..Many of these structurally diverse metabolites are derived from a family of related enzymes called polyketide synthases (PKSs)...
  9. pmc Structure and biosynthesis of heat-stable antifungal factor (HSAF), a broad-spectrum antimycotic with a novel mode of action
    Fengan Yu
    Department of Chemistry, University of Nebraska Lincoln, 729 Hamilton Hall, Lincoln, NE 68588 0304, USA
    Antimicrob Agents Chemother 51:64-72. 2007
    ..The elucidation of the chemical structure of HSAF and the identification of the genetic locus for its biosynthesis establish the foundation for future exploitation of this group of compounds as new fungicides or antifungal drugs...
  10. ncbi Evolutionary implications of bacterial polyketide synthases
    Holger Jenke-Kodama
    Humboldt University, Institute of Biology, Chausseestrasse, Berlin, Germany
    Mol Biol Evol 22:2027-39. 2005
    b>Polyketide synthases (PKS) perform a stepwise biosynthesis of diverse carbon skeletons from simple activated carboxylic acid units...
  11. ncbi Two different polyketide synthase genes are required for synthesis of zearalenone in Gibberella zeae
    Yong Tae Kim
    School of Agricultural Biotechnology and Center for Agricultural Biomaterials, Seoul National University, Seoul 151 921, Korea
    Mol Microbiol 58:1102-13. 2005
    ..zeae. This is the first published report on the molecular characterization of genes required for ZEA biosynthesis...
  12. pmc Biosynthesis of polyketide synthase extender units
    Yolande A Chan
    Department of Bacteriology, University of Wisconsin Madison, Madison, WI 53706, USA
    Nat Prod Rep 26:90-114. 2009
    This review covers the biosynthesis of extender units that are utilized for the assembly of polyketides by polyketide synthases. The metabolic origins of each of the currently known polyketide synthase extender units are covered.
  13. ncbi CLUSEAN: a computer-based framework for the automated analysis of bacterial secondary metabolite biosynthetic gene clusters
    T Weber
    Eberhard Karls Universitat Tubingen, Fakultat fur Biologie, Mikrobiologie Biotechnologie, Tubingen, Germany
    J Biotechnol 140:13-7. 2009
    ..tools, like BLAST and HMMer, with specific tools for the identification of the functional domains and motifs in nonribosomal peptide synthetases (NRPS)/type I polyketide synthases (PKS) and the prediction of specificities of NRPS.
  14. ncbi Linking chemical and microbial diversity in marine sponges: possible role for poribacteria as producers of methyl-branched fatty acids
    Thomas Hochmuth
    Kekule Institute of Organic Chemistry and Biochemistry, University of Bonn, Gerhard Domagk Strasse 1, 53121 Bonn, Germany
    Chembiochem 11:2572-8. 2010
    ..Three components of this PKS were studied in vitro, providing initial insight into its biochemistry...
  15. pmc Unraveling polyketide synthesis in members of the genus Aspergillus
    Yi Ming Chiang
    Graduate Institute of Pharmaceutical Science, Chia Nan University of Pharmacy and Science, Tainan, 71710, Taiwan, Republic of China
    Appl Microbiol Biotechnol 86:1719-36. 2010
    ..to produce a wide range of secondary metabolites including polyketides that are generated by multi-domain polyketide synthases (PKSs)...
  16. ncbi Molecular basis of cytochalasan biosynthesis in fungi: gene cluster analysis and evidence for the involvement of a PKS-NRPS hybrid synthase by RNA silencing
    Julia Schumann
    Leibniz Institute for Natural Product Research and Infection Biology, HKI, 07745 Jena, Germany
    J Am Chem Soc 129:9564-5. 2007
  17. pmc Metagenomic analysis reveals diverse polyketide synthase gene clusters in microorganisms associated with the marine sponge Discodermia dissoluta
    Andreas Schirmer
    Kosan Biosciences Inc, 3832 Bay Center Place, Hayward, CA 94545, USA
    Appl Environ Microbiol 71:4840-9. 2005
    ..PCR amplification of ketosynthase domains of type I modular polyketide synthases (PKS) from the microbial community of the marine sponge Discodermia dissoluta revealed great diversity and ..
  18. pmc Molecular genetic analysis of the orsellinic acid/F9775 gene cluster of Aspergillus nidulans
    James F Sanchez
    Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, School of Pharmacy, 1985 Zonal Avenue, Los Angeles, California 90089, USA
    Mol Biosyst 6:587-93. 2010
    ..Our deletions also yielded the bioactive metabolites gerfelin and diorcinol...
  19. ncbi Bioinformatic perspectives on NRPS/PKS megasynthases: advances and challenges
    Holger Jenke-Kodama
    Humboldt University, Institute of Biology, Department of Molecular Ecology, Chausseestr 117, 10115 Berlin, Germany
    Nat Prod Rep 26:874-83. 2009
    ..The successful translation of the knowledge obtained from bioinformatic dissection of NRPS/PKS megasynthases into new techniques for drug discovery and design remain challenges for the future...
  20. ncbi Evolution of metabolic diversity: insights from microbial polyketide synthases
    Holger Jenke-Kodama
    Humboldt University Berlin, Institute of Biology, Department of Molecular Ecology, Berlin, Germany
    Phytochemistry 70:1858-66. 2009
    ..of these secondary metabolites are produced by exceptionally large, multifunctional proteins termed polyketide synthases (PKSs)...
  21. ncbi A novel mycolactone from a clinical isolate of Mycobacterium ulcerans provides evidence for additional toxin heterogeneity as a result of specific changes in the modular polyketide synthase
    Hui Hong
    Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK
    Chembiochem 6:643-8. 2005
  22. pmc Biosynthesis of HSAF, a tetramic acid-containing macrolactam from Lysobacter enzymogenes
    Lili Lou
    Department of Chemistry, University of Nebraska Lincoln, Lincoln, Nebraska 68588, United States
    J Am Chem Soc 133:643-5. 2011
    ..These results reveal a previously unrecognized biosynthetic mechanism for hybrid PK/NRP in prokaryotic organisms...
  23. ncbi Assembly-line enzymology for polyketide and nonribosomal Peptide antibiotics: logic, machinery, and mechanisms
    Michael A Fischbach
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Chem Rev 106:3468-96. 2006
  24. pmc Natural biocombinatorics in the polyketide synthase genes of the actinobacterium Streptomyces avermitilis
    Holger Jenke-Kodama
    Department of Molecular Ecology, Institute of Biology, Humboldt University, Berlin, Germany
    PLoS Comput Biol 2:e132. 2006
    Modular polyketide synthases (PKSs) of bacteria provide an enormous reservoir of natural chemical diversity...
  25. pmc Illuminating the diversity of aromatic polyketide synthases in Aspergillus nidulans
    Manmeet Ahuja
    Department of Molecular Biosciences, University of Kansas, 1200 Sunnyside Avenue, Lawrence, Kansas 66045, United States
    J Am Chem Soc 134:8212-21. 2012
    ..This has allowed us to determine the products of eight NR-PKSs of Aspergillus nidulans, including seven novel compounds, as well as the NR-PKS genes required for the synthesis of the toxins alternariol (8) and cichorine (19)...
  26. pmc Widespread occurrence and genomic context of unusually small polyketide synthase genes in microbial consortia associated with marine sponges
    Lars Fieseler
    Research Center for Infectious Diseases, University of Wurzburg, Rontgenring 11, 97070 Wurzburg, Germany
    Appl Environ Microbiol 73:2144-55. 2007
    ..were dominated by a ubiquitously present, evolutionarily distinct, and highly sponge-specific group of polyketide synthases (PKSs)...
  27. ncbi Bioactive compounds synthesized by non-ribosomal peptide synthetases and type-I polyketide synthases discovered through genome-mining and metagenomics
    Katerina Nikolouli
    Department of Biochemistry and Biotechnology, University of Thessaly, Ploutonos 26 and Eolou, 41221, Larissa, Greece
    Biotechnol Lett 34:1393-403. 2012
    Non-ribosomal peptide synthetases (NRPS) and type-I polyketide synthases (PKS-I) are multimodular enzymes involved in biosynthesis of oligopeptide and polyketide secondary metabolites produced by microorganisms such as bacteria and fungi...
  28. ncbi Structural and functional analysis of A-type ketoreductases from the amphotericin modular polyketide synthase
    Jianting Zheng
    Department of Chemistry and Biochemistry, The University of Texas at Austin, Austin, TX 78712 0165, USA
    Structure 18:913-22. 2010
    ..Together, these results highlight the possibility of region-specific modification of polyketides through active site engineering of KRs...
  29. pmc Polymorphism of mycotoxin biosynthetic genes among Fusarium equiseti isolates from Italy and Poland
    Łukasz Stepień
    Department of Metabolomics, Institute of Plant Genetics, Polish Academy of Sciences, Strzeszynska 34, 60 479 Poznan, Poland
    J Appl Genet 53:227-36. 2012
    ..Italy and Poland) was evaluated by analysing the translation elongation factor 1α (tef-1α) sequences, two polyketide synthases from the ZEA biosynthetic pathway (PKS13 and PKS4) and the TRI5 gene from the trichothecene biosynthetic ..
  30. pmc The natural product domain seeker NaPDoS: a phylogeny based bioinformatic tool to classify secondary metabolite gene diversity
    Nadine Ziemert
    Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, La Jolla, California, United States of America
    PLoS ONE 7:e34064. 2012
    ..The results provide a rapid method to assess secondary metabolite biosynthetic gene diversity and richness in organisms or environments and a mechanism to identify genes that may be associated with uncharacterized biochemistry...
  31. doi Genome mining for novel natural product discovery
    Gregory L Challis
    Department of Chemistry, University of Warwick, Coventry CV4 7AL, U K
    J Med Chem 51:2618-28. 2008
  32. pmc Experimental mapping of soluble protein domains using a hierarchical approach
    Jean Denis Pédelacq
    CNRS IPBS Institut de Pharmacologie et de Biologie Structurale, 205 route de Narbonne, F 31077 Toulouse, France
    Nucleic Acids Res 39:e125. 2011
    ..X-ray quality crystals from the acyl-transferase (AT), dehydratase (DH) and enoyl-reductase (ER) domains have been obtained...
  33. pmc Widespread occurrence of secondary lipid biosynthesis potential in microbial lineages
    Christine N Shulse
    Division of Biological Sciences, University of California San Diego, La Jolla, California, United States of America
    PLoS ONE 6:e20146. 2011
    ..designated pfaEABCD, encode large, multi-domain protein complexes akin to type I iterative fatty acid and polyketide synthases, herein referred to as "Pfa synthases"...
  34. ncbi Identification of a hybrid PKS/NRPS required for pseurotin A biosynthesis in the human pathogen Aspergillus fumigatus
    Shubha Maiya
    University of Sheffield, Department of Molecular Biology and Biotechnology, S10 2TN, Sheffield, UK
    Chembiochem 8:1736-43. 2007
    ..It is likely that the first product of psoA is converted to pseurotin A by the products of other genes in this cluster...
  35. ncbi Polyketide synthases of bacterial symbionts in sponges--evolution-based applications in natural products research
    Thomas Hochmuth
    Kekule Institute of Organic Chemistry and Biochemistry, University of Bonn, Bonn, Germany
    Phytochemistry 70:1841-9. 2009
    ..This review summarizes recent work of our laboratory on the study of polyketide synthases (PKSs)...
  36. pmc The type I fatty acid and polyketide synthases: a tale of two megasynthases
    Stuart Smith
    Children s Hospital Oakland Research Institute, 5700 Martin Luther King Jr Way, Oakland, California 94609, USA
    Nat Prod Rep 24:1041-72. 2007
    ..In both animal fatty acid synthases and modular polyketide synthases, similar catalytic elements are covalently linked in the same order in megasynthases...
  37. ncbi Two polyketide synthase-encoding genes are required for biosynthesis of the polyketide virulence factor, T-toxin, by Cochliobolus heterostrophus
    Scott E Baker
    Torrey Mesa Research Institute, Syngenta, 3115 Merryfield Row, San Diego, CA 92121, USA
    Mol Plant Microbe Interact 19:139-49. 2006
    ..Thus, the carbon chain of each T-toxin family member likely is assembled by action of two PKSs, which produce two polyketides, one of which may act as the starter unit for biosynthesis of the mature T-toxin molecule...
  38. pmc Horizontal chromosome transfer, a mechanism for the evolution and differentiation of a plant-pathogenic fungus
    Yasunori Akagi
    Laboratory of Plant Pathology, Faculty of Agriculture, Tottori University, 4 101 Koyama Minami, Tottori 680 8553, Japan
    Eukaryot Cell 8:1732-8. 2009
    ..alternata strains by horizontal transfer of an entire pathogenicity chromosome. This could provide a possible mechanism by which new pathogens arise in nature...
  39. ncbi Heterologous production of polyketides by modular type I polyketide synthases in Escherichia coli
    Satoshi Yuzawa
    QB3 Institute, University of California, Berkeley, CA 94270, USA
    Curr Opin Biotechnol 23:727-35. 2012
    ..Here we review the current status and potential for metabolic engineering of polyketides in E. coli...
  40. ncbi Organization of the biosynthetic gene cluster for the macrolide concanamycin A in Streptomyces neyagawaensis ATCC 27449
    Stephen F Haydock
    Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, UK
    Microbiology 151:3161-9. 2005
    ....
  41. ncbi The CTB1 gene encoding a fungal polyketide synthase is required for cercosporin biosynthesis and fungal virulence of Cercospora nicotianae
    Mathias Choquer
    Citrus Research and Education Center, Institute of Food and Agricultural Sciences, University of Florida, 700 Experiment Station Road, Lake Alfred 33850, USA
    Mol Plant Microbe Interact 18:468-76. 2005
    ..and two acyl carrier protein (ACP) domains, and had high levels of similarity to many fungal type I polyketide synthases. Expression of a 6...
  42. ncbi The enzymology of polyether biosynthesis
    Tiangang Liu
    Laboratory of Microbial Metabolism and School of Life Sciences and Biotechnology, Shanghai Jiaotong University, Shanghai, China
    Methods Enzymol 459:187-214. 2009
    ..it from traditional type I modular polyketide biosynthesis: polyether backbones are assembled by modular polyketide synthases but are modified by two key enzymes, epoxidase and epoxide hydrolase, to generate the product...
  43. ncbi An iterative type I polyketide synthase PKSN catalyzes synthesis of the decaketide alternapyrone with regio-specific octa-methylation
    Isao Fujii
    Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7 3 1 Hongo, Bunkyo ku, Tokyo 113 0033, Japan
    Chem Biol 12:1301-9. 2005
    ..Labeling experiments confirmed that alternapyrone is a decaketide with octa-methylation from methionine on every C(2) unit except the third unit...
  44. pmc Genes for the biosynthesis of the fungal polyketides hypothemycin from Hypomyces subiculosus and radicicol from Pochonia chlamydosporia
    Christopher D Reeves
    Kosan Biosciences, Inc, 3832 Bay Center Place, Hayward, California 94545, USA
    Appl Environ Microbiol 74:5121-9. 2008
    ..These PKSs may provide a useful system for probing the mechanisms of fungal PKS programming...
  45. pmc A gene cluster containing two fungal polyketide synthases encodes the biosynthetic pathway for a polyketide, asperfuranone, in Aspergillus nidulans
    Yi Ming Chiang
    Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, School of Pharmacy, 1985 Zonal Avenue, Los Angeles, California 90089, USA
    J Am Chem Soc 131:2965-70. 2009
    ..Our examination of the 27 polyketide synthases (PKS) in A. nidulans revealed that one highly reduced PKS (HR-PKS, AN1034...
  46. ncbi A large gene cluster encoding peptide synthetases and polyketide synthases is involved in production of siderophores and oxidative stress response in the cyanobacterium Anabaena sp. strain PCC 7120
    Robert Jeanjean
    Université de la Méditerranée and Laboratoire de Chimie Bactérienne, CNRS UPR9043, 31 Chemin Joseph Aiguier, 13402 Marseille Cedex 20, France
    Environ Microbiol 10:2574-85. 2008
    Non-ribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs) are necessary for the production of a variety of secondary metabolites, such as siderophores involved in iron acquisition...
  47. ncbi DKxanthene biosynthesis--understanding the basis for diversity-oriented synthesis in myxobacterial secondary metabolism
    Peter Meiser
    Institut für Pharmazeutische Biotechnologie, Saarland University, Saarbrucken, Germany
    Chem Biol 15:771-81. 2008
    ....
  48. ncbi Biosynthesis of polyketides by trans-AT polyketide synthases
    Jorn Piel
    Kekule Institute of Organic Chemistry and Biochemistry, University of Bonn, Bonn, Germany
    Nat Prod Rep 27:996-1047. 2010
    This review discusses the biosynthesis of natural products that are generated by trans-AT polyketide synthases, a family of catalytically versatile enzymes that have recently been recognized as one of the major group of proteins involved ..
  49. ncbi The Botrytis cinerea phytotoxin botcinic acid requires two polyketide synthases for production and has a redundant role in virulence with botrydial
    Bérengère Dalmais
    Unité de Recherches BIOGER CPP, INRA, Avenue Lucien Brétignières, Thiverval Grignon, France
    Mol Plant Pathol 12:564-79. 2011
    ..However, double mutants that do not produce botcinic acid or botrydial (bcpks6Δbcbot2Δ) exhibit markedly reduced virulence. Hence, a redundant role of botrydial and botcinic acid in the virulence of B. cinerea has been demonstrated...
  50. ncbi Sequencing and modular analysis of the hybrid non-ribosomal peptide synthase - polyketide synthase gene cluster from the marine sponge Hymeniacidon perleve-associated bacterium Pseudoalteromonas sp. strain NJ631
    Peng Zhu
    College of Life Sciences, Zhejiang University, Hangzhou 310058, China
    Can J Microbiol 55:219-27. 2009
    ....
  51. pmc Functional analysis of environmental DNA-derived type II polyketide synthases reveals structurally diverse secondary metabolites
    Zhiyang Feng
    Laboratory of Genetically Encoded Small Molecules, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA
    Proc Natl Acad Sci U S A 108:12629-34. 2011
    ..The large-scale functional screening of eDNA clones should be a productive strategy for generating structurally previously uncharacterized chemical entities for use in future drug development efforts...
  52. pmc Priming type II polyketide synthases via a type II nonribosomal peptide synthetase mechanism
    Miho Izumikawa
    College of Pharmacy, University of Arizona, Tucson, Arizona 85721, USA
    J Am Chem Soc 128:1428-9. 2006
    ....
  53. ncbi The stereochemistry of complex polyketide biosynthesis by modular polyketide synthases
    David H Kwan
    Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC V6T 1Z1, Canada
    Molecules 16:6092-115. 2011
    Polyketides are a diverse class of medically important natural products whose biosynthesis is catalysed by polyketide synthases (PKSs), in a fashion highly analogous to fatty acid biosynthesis...
  54. ncbi Type II polyketide synthases: gaining a deeper insight into enzymatic teamwork
    Christian Hertweck
    Leibniz Institute for Natural Product Research and Infection Biology, HKI, Beutenbergstrasse 11a, 07745 Jena, Germany
    Nat Prod Rep 24:162-90. 2007
    ..This review covers advances in understanding of the biosynthesis of polyketides produced by type II PKS systems at the genetic, biochemical and structural levels...
  55. ncbi The biosynthetic logic of polyketide diversity
    Christian Hertweck
    Department of Biomolecular Chemistry, Leibniz Institute for Natural Product Research and Infection Biology, HKI, Beutenbergstr 11a, 07745 Jena, Germany
    Angew Chem Int Ed Engl 48:4688-716. 2009
    ..This review highlights recently unveiled biosynthetic mechanisms to generate highly diverse and complex molecules...
  56. ncbi Theoretical considerations and computational analysis of the complexity in polyketide synthesis pathways
    Joanna González-Lergier
    Department of Chemical and Biological Engineering, Northwestern University, Evanston, Illinois 60208, USA
    J Am Chem Soc 127:9930-8. 2005
    ..Consequently, this formulation would prove useful in guiding experimental approaches to engineer novel polyketides, a number of which will likely have medicinal properties...
  57. ncbi Cytotoxic tetramic acid derivative produced by a plant type-III polyketide synthase
    Toshiyuki Wakimoto
    Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7 3 1 Hongo, Tokyo 113 0033, Japan
    J Am Chem Soc 133:4746-9. 2011
    ..Remarkably, the novel tetramic acid dimer D-5 formed from D-phenylalanoyl-CoA showed moderate antiproliferative activity against murine leukemia P388 cells...
  58. pmc PKMiner: a database for exploring type II polyketide synthases
    Jinki Kim
    Department of Information and Communications Engineering, KAIST, Daejeon, 305 701, South Korea
    BMC Microbiol 12:169. 2012
    ..aromatic polyketides are a pharmacologically important group of natural products synthesized by type II polyketide synthases (type II PKSs) in actinobacteria...
  59. ncbi Complete biosynthesis of erythromycin A and designed analogs using E. coli as a heterologous host
    Haoran Zhang
    Department of Chemical and Biological Engineering, Tufts University, Medford, MA 02155, USA
    Chem Biol 17:1232-40. 2010
    ..Success establishes E. coli as a viable option for the heterologous production of erythromycin A and more broadly as a platform for the directed production of erythromycin analogs...
  60. ncbi Structural and functional analysis of C2-type ketoreductases from modular polyketide synthases
    Jianting Zheng
    Department of Chemistry and Biochemistry, University of Texas at Austin, Austin, TX 78712, USA
    J Mol Biol 410:105-17. 2011
    The process by which α-stereocenters of polyketide intermediates are set by modular polyketide synthases (PKSs) when condensation is not immediately followed by reduction is mysterious...
  61. ncbi MapsiDB: an integrated web database for type I polyketide synthases
    Hongseok Tae
    SmallSoft Co, Ltd, Jang Dong 59 5, Yusung Gu, Daejeon 305 343, South Korea
    Bioprocess Biosyst Eng 32:723-7. 2009
    ..They are biosynthesized from short carboxylic acid precursors by polyketide synthases (PKSs)...
  62. ncbi Characterisation of a pks gene which is expressed during ochratoxin A production by Aspergillus carbonarius
    Antonia Gallo
    Institute of Sciences of Food Production, ISPA CNR, Bari, Italy
    Int J Food Microbiol 129:8-15. 2009
    ..OTA is a potent nephrotoxin and a possible human carcinogen with a polyketide derived structure. Fungal polyketide synthases (PKSs) have recently been demonstrated to be involved in OTA biosynthesis in both Penicillium and ..
  63. pmc Enzymatic synthesis of resorcylic acid lactones by cooperation of fungal iterative polyketide synthases involved in hypothemycin biosynthesis
    Hui Zhou
    Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, California 90095, USA
    J Am Chem Soc 132:4530-1. 2010
    ..During biosynthesis, its carbon framework is assembled by two iterative polyketide synthases (PKSs), Hpm8 (highly reducing) and Hpm3 (nonreducing)...
  64. pmc Biosynthesis of the salinosporamide A polyketide synthase substrate chloroethylmalonyl-coenzyme A from S-adenosyl-L-methionine
    Alessandra S Eustáquio
    Scripps Institution of Oceanography, University of California at San Diego, La Jolla, CA 92093 0204, USA
    Proc Natl Acad Sci U S A 106:12295-300. 2009
    ..Because halogenation often increases the bioactivity of drugs, the availability of a halogenated polyketide building block may be useful in molecular engineering approaches toward polyketide scaffolds...
  65. ncbi Molecular basis of Celmer's rules: stereochemistry of catalysis by isolated ketoreductase domains from modular polyketide synthases
    Alexandros P Siskos
    Department of Biochemistry, University of Cambridge, UK
    Chem Biol 12:1145-53. 2005
    A system is reported for the recombinant expression of individual ketoreductase (KR) domains from modular polyketide synthases (PKSs) and scrutiny of their intrinsic specificity and stereospecificity toward surrogate diketide substrates...
  66. pmc Synthetic strategy of nonreducing iterative polyketide synthases and the origin of the classical "starter-unit effect"
    Jason M Crawford
    Department of Chemistry, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA
    Chembiochem 9:1019-23. 2008
  67. pmc Crystal structures of dehydratase domains from the curacin polyketide biosynthetic pathway
    David L Akey
    Life Sciences Institute and Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA
    Structure 18:94-105. 2010
    Modular polyketide synthases (PKS) make novel natural products through a series of preprogrammed chemical steps catalyzed by an assembly line of multidomain modules...
  68. ncbi Polyketides, proteins and genes in fungi: programmed nano-machines begin to reveal their secrets
    Russell J Cox
    School of Chemistry, University of Bristol, Cantock s Close, Bristol, UK BS8 1TS
    Org Biomol Chem 5:2010-26. 2007
    ..These compounds are synthesised by highly programmed and very large iterative multifunctional proteins, the polyketide synthases, with nm dimensions...
  69. pmc Polyketide synthase gene responsible for citrinin biosynthesis in Monascus purpureus
    Takeo Shimizu
    International Center for Biotechnology, Osaka University, 2 1 Yamadaoka, Suita, Osaka 565 0871, Japan
    Appl Environ Microbiol 71:3453-7. 2005
    ..purpureus...
  70. ncbi The chemical biology of modular biosynthetic enzymes
    Jordan L Meier
    Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093 0358, USA
    Chem Soc Rev 38:2012-45. 2009
    ....
  71. pmc The Pks13/FadD32 crosstalk for the biosynthesis of mycolic acids in Mycobacterium tuberculosis
    Sabine Gavalda
    CNRS, IPBS Institut de Pharmacologie et de Biologie Structurale, Départements Mécanismes Moléculaires des Infections Mycobacteriennes, Biologie du Cancer, 205 route de Narbonne, F 31077 Toulouse, France
    J Biol Chem 284:19255-64. 2009
    ..Pks13 ultimately condenses the two loaded fatty acyl chains to produce alpha-alkyl beta-ketoacids, the precursors of mycolic acids. The developed in vitro assay will constitute a strategic tool for antimycobacterial drug screening...
  72. pmc Complete reconstitution of a highly reducing iterative polyketide synthase
    Suzanne M Ma
    Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, CA 90095, USA
    Science 326:589-92. 2009
    Highly reducing iterative polyketide synthases are large, multifunctional enzymes that make important metabolites in fungi, such as lovastatin, a cholesterol-lowering drug from Aspergillus terreus...
  73. ncbi Evolution and taxonomic distribution of nonribosomal peptide and polyketide synthases
    Grigoris D Amoutzias
    Department of Plant Systems Biology, VIB and Department of Molecular Genetics, Ghent University, Technologiepark 927, B 9052 Ghent, Belgium
    Future Microbiol 3:361-70. 2008
    The majority of nonribosomal peptide synthases and type I polyketide synthases are multimodular megasynthases of oligopeptide and polyketide secondary metabolites, respectively...
  74. ncbi Carrier protein structure and recognition in polyketide and nonribosomal peptide biosynthesis
    Jonathan R Lai
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA
    Biochemistry 45:14869-79. 2006
    ....
  75. ncbi Evidence for a novel phosphopantetheinyl transferase domain in the polyketide synthase for enediyne biosynthesis
    Elavazhagan Murugan
    Division of Chemical Biology and Biotechnology, School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore
    FEBS Lett 582:1097-103. 2008
    ..The results revealed a novel type of PPTase with unique structure and substrate specificity, and suggested that the polyketide synthase probably acquired the PPTase domain from a primary metabolic pathway in evolution...
  76. pmc Polyketide decarboxylative chain termination preceded by o-sulfonation in curacin a biosynthesis
    Liangcai Gu
    Life Sciences Institute, Department of Medicinal Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA
    J Am Chem Soc 131:16033-5. 2009
    ....
  77. pmc Characterization of two polyketide synthase genes involved in zearalenone biosynthesis in Gibberella zeae
    Iffa Gaffoor
    Department of Plant Biology, Michigan State University, East Lansing, MI 48824, USA
    Appl Environ Microbiol 72:1793-9. 2006
    ..We cloned two genes, designated ZEA1 and ZEA2, which encode polyketide synthases that participate in the biosynthesis of zearalenone by Gibberella zeae (anamorph Fusarium graminearum)...
  78. pmc ASMPKS: an analysis system for modular polyketide synthases
    Hongseok Tae
    Information Technology Institute, SmallSoft Co, Ltd, Jang Dong 59 5, Yusung Gu, Daejeon 305 343, South Korea
    BMC Bioinformatics 8:327. 2007
    ..Moreover, the increasing use of genetic engineering to research new kinds of polyketides requires genome wide analysis...
  79. ncbi Structures and mechanisms of polyketide synthases
    Chaitan Khosla
    Stanford University, Stanford, California 94305 5080, USA
    J Org Chem 74:6416-20. 2009
    ..This in turn facilitated rapid cloning and sequencing of genes encoding a number of polyketide synthases (PKSs)...
  80. ncbi Structural insight into chain-length control and product specificity of pentaketide chromone synthase from Aloe arborescens
    Hiroyuki Morita
    Mitsubishi Kagaku Institute of Life Sciences MITILS, 11 Minamiooya, Machida, Tokyo 194 8511, Japan
    Chem Biol 14:359-69. 2007
    ..These findings not only provided insight into the polyketide formation reaction, but they also suggested strategies for the engineered biosynthesis of polyketides...
  81. ncbi Isolation and purification of a new kalimantacin/batumin-related polyketide antibiotic and elucidation of its biosynthesis gene cluster
    Wesley Mattheus
    Laboratory of Gene Technology, Katholieke Universiteit Leuven, Leuven B 3000, Belgium
    Chem Biol 17:149-59. 2010
    ..This makes it a promising new therapeutic option to cope with multidrug-resistant clinical infections...
  82. ncbi Rational design and assembly of synthetic trimodular polyketide synthases
    Hugo G Menzella
    Kosan Biosciences Inc, Hayward, CA 94545, USA
    Chem Biol 14:143-51. 2007
    Type I polyketide synthases (PKSs) consist of modules that add two-carbon units in polyketide backbones...
  83. pmc The biochemical basis for stereochemical control in polyketide biosynthesis
    Chiara R Valenzano
    Department of Chemistry, Box H, Brown University, Providence, Rhode Island 02912 9108, USA
    J Am Chem Soc 131:18501-11. 2009
    ..centers, a series of incubations was carried out using reconstituted components from a variety of modular polyketide synthases. In all cases the stereochemistry of the product was directly correlated with the intrinsic ..
  84. ncbi Multifactorial induction of an orphan PKS-NRPS gene cluster in Aspergillus terreus
    Markus Gressler
    Microbial Biochemistry and Physiology, Leibniz Institute for Natural Product Research and Infection Biology e V, Hans Knoell Institute, Beutenbergstrasse 11a, Jena, Germany
    Chem Biol 18:198-209. 2011
    ..Gene inactivation and stable isotope labeling experiments unveiled the molecular basis for flavipucine/fruit rot toxin biosynthesis...
  85. ncbi Directed mutagenesis alters the stereochemistry of catalysis by isolated ketoreductase domains from the erythromycin polyketide synthase
    Abel Baerga-Ortiz
    Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, United Kingdom
    Chem Biol 13:277-85. 2006
    ..These data confirm the role of key residues in stereocontrol and suggest an additional way to make rational alterations in polyketide antibiotic structure...
  86. pmc Crystal structure of the erythromycin polyketide synthase dehydratase
    Adrian Keatinge-Clay
    Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA 94158, USA
    J Mol Biol 384:941-53. 2008
    The dehydratases (DHs) of modular polyketide synthases (PKSs) catalyze dehydrations that occur frequently in the biosynthesis of complex polyketides, yet little is known about them structurally or mechanistically...
  87. ncbi Octaketide-producing type III polyketide synthase from Hypericum perforatum is expressed in dark glands accumulating hypericins
    Katja Karppinen
    Department of Biology, University of Oulu, Finland
    FEBS J 275:4329-42. 2008
    ..Based on our results, HpPKS2 may have a role in the biosynthesis of hypericins in H. perforatum but some additional factors are possibly required for the production of emodin anthrone in vivo...
  88. ncbi Cloning and functional analysis of the naphthomycin biosynthetic gene cluster in Streptomyces sp. CS
    Yingying Wu
    State Key Laboratory of Microbial Metabolism, and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China
    Mol Biosyst 7:2459-69. 2011
    ..The information presented here expands our understanding of the biosynthesis of naphthalenic ansamycins, and may pave the way for engineering ansamacrolactams with improved pharmaceutical properties...
  89. pmc Unusual activities of the thioesterase domain for the biosynthesis of the polycyclic tetramate macrolactam HSAF in Lysobacter enzymogenes C3
    Lili Lou
    Department of Chemistry, University of Nebraska, Lincoln, Nebraska 68588, United States
    Biochemistry 51:4-6. 2012
    ..The iterative PKS-NRPS is found in all polycyclic tetramate macrolactam gene clusters, and the unusual activities of the TE may be common to this type of hybrid PKS-NRPS...
  90. pmc Hydroxymalonyl-acyl carrier protein (ACP) and aminomalonyl-ACP are two additional type I polyketide synthase extender units
    Yolande A Chan
    Department of Bacteriology, University of Wisconsin, Madison, WI 53706, USA
    Proc Natl Acad Sci U S A 103:14349-54. 2006
    Combinatorial biosynthesis of type I polyketide synthases is a promising approach for the generation of new structural derivatives of polyketide-containing natural products...
  91. ncbi High-throughput mutagenesis to evaluate models of stereochemical control in ketoreductase domains from the erythromycin polyketide synthase
    Helen M O'Hare
    Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, United Kingdom
    Chem Biol 13:287-96. 2006
    Ketoreductase (KR) activities help determine the stereochemistry of the products of modular polyketide synthases (PKSs)...
  92. ncbi Fungal type I polyketide synthases
    Russell J Cox
    School of Chemistry, University of Bristol, Bristol, United Kingdom
    Methods Enzymol 459:49-78. 2009
    ..These are produced by very large multifunctional iterative enzymes, the iterative type I polyketide synthases (PKSs) whose closest structural and functional analogues are the mammalian fatty acid synthases...
  93. ncbi Rational domain swaps decipher programming in fungal highly reducing polyketide synthases and resurrect an extinct metabolite
    Katja M Fisch
    School of Chemistry, University of Bristol, Cantock s Close, Bristol BS8 1TS, UK
    J Am Chem Soc 133:16635-41. 2011
    The mechanism of programming of iterative highly reducing polyketide synthases remains one of the key unsolved problems of secondary metabolism...
  94. pmc Dehydratase-specific probes for fatty acid and polyketide synthases
    Fumihiro Ishikawa
    Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093 0358, USA
    J Am Chem Soc 134:769-72. 2012
    ..can facilitate detection, enrichment, and identification of DH enzymes in fatty acid synthases (FASs) and polyketide synthases (PKSs)...
  95. pmc Combinatorial polyketide biosynthesis at higher stage
    Holger Jenke-Kodama
    Mol Syst Biol 1:2005.0025. 2005
  96. ncbi Mutagenesis of a modular polyketide synthase enoylreductase domain reveals insights into catalysis and stereospecificity
    David H Kwan
    Department of Biochemistry, University of Cambridge, United Kingdom
    ACS Chem Biol 5:829-38. 2010
    Modular type I polyketide synthases (PKSs) such as the 6-deoxyerythronolide B synthase (DEBS) or the rapamycin synthase (RAPS) biosynthesize their polyketide products in a fashion similar to fatty acid biosynthesis...
  97. ncbi Prediction and manipulation of the stereochemistry of enoylreduction in modular polyketide synthases
    David H Kwan
    Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, UK
    Chem Biol 15:1231-40. 2008
    ..In contrast, alteration (Val to Tyr) at this position in a rapamycin-derived PKS ER was insufficient to achieve a switch from R to S, showing that additional residues also participate in stereocontrol of enoylreduction...
  98. ncbi Employing modular polyketide synthase ketoreductases as biocatalysts in the preparative chemoenzymatic syntheses of diketide chiral building blocks
    Shawn K Piasecki
    Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX 78712, USA
    Chem Biol 18:1331-40. 2011
    ..Several biocatalytic reactions were scaled up to yield more than 100 mg of product. These syntheses demonstrate the ability of PKS enzymes to economically and greenly generate diverse chiral building blocks on a preparative scale...
  99. ncbi Genetic approaches to polyketide antibiotics. 1
    Robert McDaniel
    Kosan Biosciences, 3832 Bay Center Place, Hayward, California 94545, USA
    Chem Rev 105:543-58. 2005
  100. ncbi Hybrid nonribosomal peptide-polyketide interfaces in epothilone biosynthesis: minimal requirements at N and C termini of EpoB for elongation
    Fei Liu
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    Chem Biol 11:1533-42. 2004
    ..is a hybrid natural product produced by the combined action of nonribosomal peptide synthetases (NRPS) and polyketide synthases (PKS)...
  101. ncbi Chapter 9. Synthetic probes for polyketide and nonribosomal peptide biosynthetic enzymes
    Jordan L Meier
    Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California, USA
    Methods Enzymol 458:219-54. 2009
    ..The continued development and application of these methods has the potential to greatly complement our current approaches to the study of natural product biosynthesis...

Research Grants62

  1. Fungal Polyketide Synthases and Environmental Toxin Biosynthesis
    CRAIG ARTHUR TOWNSEND; Fiscal Year: 2013
    ..These secondary metabolites all derive from a family of fungal, polydomain enzymes called polyketide synthases (PKSs)...
  2. Biosynthesis of Microbial Polyketides
    David E Cane; Fiscal Year: 2013
    ..Indeed, modular polyketide synthases are among the largest and most complex biological catalysts that are known...
  3. A Robust Platform for Reconstituting and Engineering Iterative Megasynthases
    Yi Tang; Fiscal Year: 2012
    ..Among the most interesting but least understood enzymes making these compounds are the iterative polyketide synthases (IPKSs) found in filamentous fungi...
  4. Mass Spectrometric Studies of Thiotemplate Biosynthesis
    Neil L Kelleher; Fiscal Year: 2013
    ..anticancer and antifungal properties are synthesized by non-ribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs), yet most microbes do not express the great majority of their NRPS or PKS enzymes...
  5. Structural basis of specificity in affinity-labeled polyketide synthase didomains
    Janet L Smith; Fiscal Year: 2012
    ..PUBLIC HEALTH RELEVANCE: Complex mega-enzyme machines known as polyketide synthases (PKS) produce many antibiotics and other bio-active molecules...
  6. Structural Biology of Complex Enzymes
    Janet L Smith; Fiscal Year: 2013
    ..This project continues the structural study of polyketide synthases and glutamine amidotransferases...
  7. Molecular Analysis of Modular Polyketide Synthases
    Janet L Smith; Fiscal Year: 2013
    ..Specific aims include: I. Molecular Analysis of Modular Polyketide Synthases. Design and employ synthetic substrates and Pik, DEBS, and Tyl terminal modules to explore selectivity and ..
  8. Synthetic Biology Approach to Regioselectively Modified Polyketides
    Gavin J Williams; Fiscal Year: 2013
    ..biological activities of polyketides are determined by their chemical structures, which are constructed by polyketide synthases (PKSs)...
  9. Characterization and Engineering of Fungal Megasynthases in Escherichia coli
    Yi Tang; Fiscal Year: 2012
    ..Iterative fungal polyketide synthases (PKSs) use a unique set of biochemical rules in the synthesis of complex polyketides...
  10. Enzyme Discovery for Natural Product Biosynthesis
    GEORGE NEAL PHILLIPS; Fiscal Year: 2013
    ..For example, new biosynthetic routes are being built around engineered systems such as the modular polyketide synthases to produce new compounds...
  11. Phoslactomycins: Biosynthesis & Activity
    Kevin A Reynolds; Fiscal Year: 2010
    ..It has been shown that both natural products are generated by modular polyketide synthases (PKSs). In the case of PLM much of the biosynthetic process has been deciphered...
  12. Phoslactomycins: Biosynthesis &Activity
    Kevin A Reynolds; Fiscal Year: 2013
    ..It has been shown that both natural products are generated by modular polyketide synthases (PKSs). In the case of PLM much of the biosynthetic process has been deciphered...
  13. FUNGAL POLYKETIDE SYNTHASES
    CHARLES SIH; Fiscal Year: 2001
    As our long-term goal, we will attempt to provide the understanding needed to design new polyketide synthases (PKSs) with novel properties, by characterizing the physical and functional nature of the fungal PKSs involved in the ..
  14. Mechanistic analysis of 6-deoxyerythronolide B synthase
    LOUISE KARINE CHARKOUDIAN; Fiscal Year: 2011
    ..and rich in stereochemistry, are elegantly synthesized in biological systems via a predictable modular polyketide synthases (PKSs) paradigm...
  15. ENGINEERING PRECURSOR SUPPLY FOR POLYKETIDE BIOSYNTHESIS
    Kevin Reynolds; Fiscal Year: 2003
    Polyketides are a group of extremely diverse natural products produced by polyketide synthases (PKSs)...
  16. Structure, Mechanism, and Engineering of Assembly Line Polyketide Synthases
    Chaitan Khosla; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Multimodular polyketide synthases (PKSs) are enzymatic assembly lines that synthesize many antibiotics...
  17. Control of Initiation of Development in M. xanthus
    Mitchell Singer; Fiscal Year: 2006
    ..Large multienzyme complexes termed polyketide synthases and peptide synthetases, many of which are produced during starvation, synthesize many of these compounds...
  18. BIOSYNTHESIS OF POLYETHER ANTIBIOTICS
    Charles Hutchinson; Fiscal Year: 1992
    ..assemble the intricate carbon skeleton of polyether antibiotics by studying the properties of polyether polyketide synthases and the corresponding genes...
  19. MOLECULAR ANALYSIS OF POLYKETIDE SYNTHASE GENES
    David Hopwood; Fiscal Year: 1990
    ..by site-directed mutagenesis, and in vitro recombination between DNA coding for parts of different polyketide synthases to produce "hybrid" antibiotics...
  20. Proteomic methodologies for polyketide biosynthesis (RMI)
    MICHAEL BURKART; Fiscal Year: 2007
    ..by applicant): This project develops new tools for the identification, isolation, and characterization of polyketide synthases from producer organisms...
  21. Type III Polyketide Synthases: Structure and Mechanism
    BRADLEY MOORE; Fiscal Year: 2006
    ..These small aromatic polyketides are synthesized by homodimeric (type III) polyketide synthases (PKSs) that are phylogenetically and biochemically related to ubiquitous plant PKSs such as chalcone ..
  22. AT-less Type I Polyketide Synthases
    Ben Shen; Fiscal Year: 2013
    ....
  23. BIOSYNTHESIS OF AROMATIC POLYKETIDES
    CHARLES SIH; Fiscal Year: 2001
    ..b) Analyze the mechanism of fungal polyketide synthases and cyclases by studying the properties of hybrid sets of PKS genes containing combinations of the 6MSAS, ..
  24. Engineering Biosynthesis of Brefeldin A and Its Analogs
    Weiwen Zhang; Fiscal Year: 2002
    Polyketides are a group of extremely diverse natural products produced by polyketide synthases (PKSs)...
  25. Efficient Synthesis of (+)-Discodermolide
    David Myles; Fiscal Year: 2001
    ..a process to prepare an equivalent of this common precursor by fermentation, using genetically engineered polyketide synthases. In Phase 1, we will develop the methods to prepare this material and demonstrate its utility by conversion ..
  26. Mutant Acyltransferases in Natural Product Biosynthesis
    ANDREW KOPPISCH; Fiscal Year: 2003
    Bacterial aromatic polyketide synthases (PKS) are multi-functional enzyme complexes responsible for the biosynthesis of numerous biologically and medicinally important molecules...
  27. Biosynthesis of the Antibiotic Polyketide Enterocin
    BRADLEY MOORE; Fiscal Year: 2005
    ..A basic understanding of aromatic polyketide assembly catalyzed by iterative type II polyketide synthases (PKSs) at the biochemical and structural levels will undoubtedly increase our appreciation for these ..
  28. Structural /Mechanistic Study of Lantibiotic Biosynthetic Enzymes & Autoimmunity
    Satish K Nair; Fiscal Year: 2010
    ..work in biosynthetic combinatorial chemistry technology has already established the utility of bacterial polyketide synthases and nonribosomal peptide synthases in generating natural and un-natural products with antibiotic ..
  29. Mechanistic Analysis of NRPS Cyclization Domains
    WENDY KELLY; Fiscal Year: 2006
    Nonribosomal peptide synthetases (NRPS) and polyketide synthases (PKS) generate a vast number of clinically relevant natural products. These modular systems are amenable to genetic engineering to generate novel metabolites...
  30. Recognition Specificity in Modular Polyketide Synthases
    NATHAN SCHNARR; Fiscal Year: 2006
    ..Polyketides are a pharmalogically important class of natural products biosynthetically produced by polyketide synthases (PKSs)...
  31. Specificity of Modular Polyketide Synthases
    JEFFREY KITTENDORF; Fiscal Year: 2007
    unreadable] DESCRIPTION (provided by applicant): Bacterial type I modular polyketide synthases (PKSs) are complex, multifunctional enzymes that synthesize structurally diverse and medicinally relevant natural products...
  32. The Role of RapP in the Biosynthesis of Rapamycin
    GREGORY GATTO; Fiscal Year: 2005
    ..a macrocyclic natural product with potent immunosuppressive properties, is synthesized by a combination of polyketide synthases (PKSs) and RapP, a nonribosomal peptide synthetase (NRPS)...
  33. Enzymology of NRPS and PKS proteins by mass spectrometry
    Pieter Dorrestein; Fiscal Year: 2006
    ..for the detection of transient covalent modifications of non-ribosomal-petide synthetases (NRPS) and polyketide synthases. Initially, a general protocol will be developed for the rapid identification of the acyl domains...
  34. RIFAMYCIN BIOSYNTHETIC ANALOGS
    Chaitan Khosla; Fiscal Year: 2003
    ..6) Engineer the rifamycin gene cluster for overproduction of rifamycin B and eventual rifamycin analogs. (7) If necessary, move some of the rifamycin gene cluster into Streptomyces lividans to facilitate aims 4 - 6. ..
  35. Fatty Acid Biosynthesis in Cryptosporidium parvum
    Guan Zhu; Fiscal Year: 2010
    ..3) To validate that fatty acid metabolic enzymes may serve as rational drug target in Cryptosporidium by discovering inhibitors selectively against, parasite fatty acid metabolic enzymes. ..
  36. ENGINEERED BIOSYNTHESIS OF NOVEL MACROLACTONE POLYKETIDE
    Chaitan Khosla; Fiscal Year: 2008
    Modular polyketide synthases (PKSs) are remarkable multifunctional enzyme assemblies that synthesize numerous structurally complex and medicinally important natural products...
  37. Cryptosporidium parvum DNA replication proteins
    Guan Zhu; Fiscal Year: 2004
    ..The completion of these aims will not only prove or refute our hypothesis, but also establish a new foundation for the drug discovery targeting the parasite unique DNA mechanism machinery. ..
  38. Structure-Based Design of HLA-DQ2 Ligands
    Chaitan Khosla; Fiscal Year: 2005
    ..More generally, it provides a unique opportunity to validate class II MHC proteins as attractive therapeutic targets for autoimmune disorders. ..
  39. Enediyne Antitumor Antibiotic Synthesis - Streptomycetes
    Ben Shen; Fiscal Year: 2005
    ..shedding light on rational engineering of enediyne biosynthesis in these as well as other enediyne-producing organisms, and could realistically lead to the making of fundamentally new, clinically useful antitumor agents ..
  40. Metabolic Engineering of Yeast for Polyketide Production
    JAMES KEALEY; Fiscal Year: 2002
    ..of at least three compatible plasmids; and (iii) will permit radioactive labeling of -CoA pools and polyketide synthases. (b) Demonstrate that such a strain can express a modular polyketide synthase and produce a complex ..
  41. DEOXYHEXOSE BIOSYNTHESIS
    HEINZ FLOSS; Fiscal Year: 2002
    ..This work will lay one of the foundations for the combinatorial enzymatic synthesis of new, unnatural glycosides representing new combinations of antibiotic sugars and aglycones. ..
  42. BIOLOGICALLY ACTIVE MICROBIAL METABOLITES
    HEINZ FLOSS; Fiscal Year: 2003
    ....
  43. 7th US-Japan Seminar on Biosyntyhesis of Natural Products 6/22-26/2008
    Ben Shen; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  44. Biosynthesis of hybrid peptide-polyketide antibiotics
    Ben Shen; Fiscal Year: 2007
    Nonribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs) have been exploited successfully in combinatorial biosynthesis of "unnatural" natural products for drug lead discovery and optimization...
  45. Technologies for the rapid engineering of bacterial chromosomes with synthetic DN
    JAMES KEALEY; Fiscal Year: 2007
    ....
  46. Leptomycin B Development for Cancer Therapy
    Charles Hutchinson; Fiscal Year: 2004
    ..coelicolor, we will proceed with preclinical development of LMB or the discovery and development of an LMB analog in Phase II research. ..
  47. STRUCTURAL STUDY OF EUKARYOTIC TRANSCRIPTION REGULATION
    Francisco Asturias; Fiscal Year: 2004
    ..By identifying structural differences and similarities between the complexes we hope to contribute to the understanding of what increasingly appears as a universal mechanism for transcription control. ..
  48. CONFORMATION ACTIVITY RELATIONSHIPS
    Richard Taylor; Fiscal Year: 2003
    ..This increased understanding of epothilone's mode of action at the molecular level will allow for the preparation of the next generation of microtubule-stabilizing anti-mitotic agents. ..
  49. Combinatorial Biosynthesis of Polyketides
    DANIEL SANTI; Fiscal Year: 2005
    ....
  50. Chemoenzymatic analysis of bryostatin biosynthesis
    Nicole Lopanik; Fiscal Year: 2007
    ..This research may lead to production of bryostatin by a heterologous host. ..
  51. Discodermolide Biosynthesis Genes
    Charles Hutchinson; Fiscal Year: 2002
    ..Our research will also establish the technological base for a general approach to making many other currently scarce marine polyketides with anti-tumor activity available in large amounts for drug development. ..
  52. Laulimalide Production Genes
    Charles Hutchinson; Fiscal Year: 2003
    ..halichondrins, laulimalide and other marine cytotoxins, which are made by pathways involving polyketide synthases, have been hampered by inadequate supplies of the marine polyketides because they are available only by ..
  53. BIOCHEMISTRY AND MOLECULAR GENETICS OF MITOMYCIN BIOSYNT
    David Sherman; Fiscal Year: 2003
    ..Overall, this work will provide an important theoretical and experimental base for future combinatorial biology-based production of novel AHBA-derived natural products using molecular genetic technology. ..
  54. MINORITY PREDOCTORAL FELLOWSHIP PROGRAM
    Kenolisa Onwueme; Fiscal Year: 2006
    ..Our ultimate aim is to clarify roles of microbial metabolites in pathogenesis and virulence with a view to discover novel targets for therapeutic intervention in infectious disease processes. ..
  55. MYRIAPORONES: SYNTHETIC AND BIOLOGICAL STUDIES
    Richard Taylor; Fiscal Year: 2003
    ..abstract_text> ..
  56. Genomic Analysis of Antibiotic Biosynthesis
    David Sherman; Fiscal Year: 2005
    ..coelicolor genome. ..
  57. Human mitochondrial fatty acid synthase
    Stuart Smith; Fiscal Year: 2009
    ..Elucidation of the role of the mitFAS system in mitochondrial function may aid in understanding the etiology of these disorders. ..
  58. Virulence-conferring siderophore biosynthesis inhibitors
    LUIS QUADRI; Fiscal Year: 2006
    ..These antimicrobials will constitute a base for subsequent studies for the development of new drugs that, alone or in combination therapies, are anticipated to be useful in the treatment of MDR Yp and Mb infections. ..