L Heide

Summary

Country: Germany

Publications

  1. doi request reprint New aminocoumarin antibiotics as gyrase inhibitors
    Lutz Heide
    Pharmaceutical Institute, Eberhard Karls Universitat Tubingen, Auf der Morgenstelle 8, 72076 Tubingen, Germany Electronic address
    Int J Med Microbiol 304:31-6. 2014
  2. doi request reprint Prenyl transfer to aromatic substrates: genetics and enzymology
    Lutz Heide
    Pharmazeutische Biologie, Pharmazeutisches Institut, Eberhard Karls Universitat Tubingen, Auf der Morgenstelle 8, 72076 Tubingen, Germany
    Curr Opin Chem Biol 13:171-9. 2009
  3. ncbi request reprint Randomized controlled trial of a traditional preparation of Artemisia annua L. (Annual Wormwood) in the treatment of malaria
    Markus S Mueller
    German Institute for Medical Mission, P O Box 1307, 72003 Tübingen, Germany
    Trans R Soc Trop Med Hyg 98:318-21. 2004
  4. doi request reprint Use of a halogenase of hormaomycin biosynthesis for formation of new clorobiocin analogues with 5-chloropyrrole moieties
    Lutz Heide
    Pharmazeutische Biologie, Pharmazeutisches Institut, Eberhard Karls Universitat Tubingen, Auf der Morgenstelle 8, 72076 Tubingen, Germany
    Chembiochem 9:1992-9. 2008
  5. ncbi request reprint Combinatorial biosynthesis, metabolic engineering and mutasynthesis for the generation of new aminocoumarin antibiotics
    L Heide
    Pharmaceutical Institute, University of Tubingen, Germany
    Curr Top Med Chem 8:667-79. 2008
  6. doi request reprint Genetic engineering of antibiotic biosynthesis for the generation of new aminocoumarins
    Lutz Heide
    Pharmaceutical Biology, Pharmaceutical Institute, Tubingen University, Auf der Morgenstelle 8, 72076 Tubingen, Germany
    Biotechnol Adv 27:1006-14. 2009
  7. pmc CloQ, a prenyltransferase involved in clorobiocin biosynthesis
    Florence Pojer
    Pharmazeutische Biologie, Auf der Morgenstelle 8, Universitat Tubingen, 72076 Tubingen, Germany
    Proc Natl Acad Sci U S A 100:2316-21. 2003
  8. ncbi request reprint Genetic analysis of the biosynthesis of the pyrrole and carbamoyl moieties of coumermycin A1 and novobiocin
    H Xu
    Pharmazeutische Biologie, Pharmazeutisches Institut, Eberhard Karls Universitat Tubingen, Auf der Morgenstelle 8, 72076 Tubingen, Germany
    Mol Genet Genomics 268:387-96. 2002
  9. doi request reprint novE and novG act as positive regulators of novobiocin biosynthesis
    Volker Dangel
    Pharmaceutical Biology, Pharmaceutical Institute, Eberhard Karls Universitat Tubingen, Auf der Morgenstelle 8, 72076 Tubingen, Germany
    Arch Microbiol 190:509-19. 2008
  10. ncbi request reprint New aminocoumarin antibiotics from genetically engineered Streptomyces strains
    S M Li
    Pharmazeutische Biologie, Pharmazeutisches Institut, Eberhard Karls Universitat Tubingen, Auf der Morgenstelle 8, 72076 Tubingen, Germany
    Curr Med Chem 12:419-27. 2005

Collaborators

  • Shu Ming Li
  • K F Chater
  • Hans Peter Fiedler
  • Hui Xu
  • S K Katiyar
  • Klaus Dietz
  • Jorn Piel
  • Bernd Kammerer
  • Steffen Borrmann
  • Bertolt Gust
  • Jose A Salas
  • K Yazaki
  • Christopher Walsh
  • Gerhard Bringmann
  • Stefan A Laufer
  • Christoph H Blanke
  • Ludger A Wessjohann
  • Alessandra S Eustáquio
  • Anja Freitag
  • Christine Anderle
  • Volker Dangel
  • Ute Galm
  • Florence Pojer
  • Yvonne Haagen
  • Lucia Westrich
  • Elisabeth Schmutz
  • Orwah Saleh
  • Manuel Wolpert
  • Sascha Keller
  • Ruth H Flatman
  • Stefanie Siebenberg
  • Caren L Freel Meyers
  • Thomas Luft
  • Anthony Maxwell
  • Xin Qing Zhao
  • Katrin Flinspach
  • Elisa Haug-Schifferdecker
  • Irmela Wagner
  • Jurgen Schmidt
  • Ute Metzger
  • Inge Unsöld
  • Malcolm Page
  • David M Lawson
  • Susanne Hennig
  • Ta Thi Thu Thuy
  • Karin Räth
  • Emmanuel Wemakor
  • Markus Oberthür
  • Markus S Mueller
  • Daniel Kahne
  • Christoph H Gleiter
  • Annegret Köhle
  • Reinhard Brückner
  • Mervyn Bibb
  • Leonard Kaysser
  • Margaret C M Smith
  • Anna Eliasson Lantz
  • Deniz Arican
  • M Steffensky
  • Juan Pablo Gomez-Escribano
  • Prashant M Bapat
  • Georg Zocher
  • Christiane Wolz
  • Johannes Härle
  • Christoph Schall
  • Edyta Stec
  • Jean Luc Pernodet
  • Björn Boll
  • Christiane Goerke
  • Thilo Stehle
  • Kerstin Seeger
  • Martin Stieger
  • Matthew Burrell
  • Stefan Reinelt
  • Joseph P Noel
  • Stéphane B Richard
  • Tanja Gulder
  • Silke Alt
  • Katja Fay
  • Kerstin Glück
  • Carmen Mendez
  • Alessandra Eustaquio
  • Chun Gyu Kim
  • Hei Chan Lee
  • Heike Rapp
  • Holger Scheible
  • Jae Kyung Sohng
  • Alison J Howells
  • Stefanie Heller
  • Gitta Walz

Detail Information

Publications67

  1. doi request reprint New aminocoumarin antibiotics as gyrase inhibitors
    Lutz Heide
    Pharmaceutical Institute, Eberhard Karls Universitat Tubingen, Auf der Morgenstelle 8, 72076 Tubingen, Germany Electronic address
    Int J Med Microbiol 304:31-6. 2014
    ..aureus. Therefore, a combination of aminocoumarins and fluoroquinolones strongly reduced the risk of resistance development and may offer new prospects in anti-infective therapy. ..
  2. doi request reprint Prenyl transfer to aromatic substrates: genetics and enzymology
    Lutz Heide
    Pharmazeutische Biologie, Pharmazeutisches Institut, Eberhard Karls Universitat Tubingen, Auf der Morgenstelle 8, 72076 Tubingen, Germany
    Curr Opin Chem Biol 13:171-9. 2009
    ..In fungi, a group of closely related indole prenyltransferase was found to carry out aromatic prenylations with different substrate specificity and regiospecificity, and to catalyze both regular and reverse prenylations...
  3. ncbi request reprint Randomized controlled trial of a traditional preparation of Artemisia annua L. (Annual Wormwood) in the treatment of malaria
    Markus S Mueller
    German Institute for Medical Mission, P O Box 1307, 72003 Tübingen, Germany
    Trans R Soc Trop Med Hyg 98:318-21. 2004
    ..However, recrudescence rates were high in the Artemisia groups. Therefore, monotherapy with Artemisia annua L. cannot be recommended as alternative to modern antimalarials, but may deserve further investigation...
  4. doi request reprint Use of a halogenase of hormaomycin biosynthesis for formation of new clorobiocin analogues with 5-chloropyrrole moieties
    Lutz Heide
    Pharmazeutische Biologie, Pharmazeutisches Institut, Eberhard Karls Universitat Tubingen, Auf der Morgenstelle 8, 72076 Tubingen, Germany
    Chembiochem 9:1992-9. 2008
    ..If this assumption is true, this study presents the first experiment in combinatorial biosynthesis that uses a halogenase that acts on an acyl carrier protein-bound substrate...
  5. ncbi request reprint Combinatorial biosynthesis, metabolic engineering and mutasynthesis for the generation of new aminocoumarin antibiotics
    L Heide
    Pharmaceutical Institute, University of Tubingen, Germany
    Curr Top Med Chem 8:667-79. 2008
    ....
  6. doi request reprint Genetic engineering of antibiotic biosynthesis for the generation of new aminocoumarins
    Lutz Heide
    Pharmaceutical Biology, Pharmaceutical Institute, Tubingen University, Auf der Morgenstelle 8, 72076 Tubingen, Germany
    Biotechnol Adv 27:1006-14. 2009
    ....
  7. pmc CloQ, a prenyltransferase involved in clorobiocin biosynthesis
    Florence Pojer
    Pharmazeutische Biologie, Auf der Morgenstelle 8, Universitat Tubingen, 72076 Tubingen, Germany
    Proc Natl Acad Sci U S A 100:2316-21. 2003
    ..CloQ and the similar NovQ from the novobiocin producer seem to belong to a new class of prenyltransferases...
  8. ncbi request reprint Genetic analysis of the biosynthesis of the pyrrole and carbamoyl moieties of coumermycin A1 and novobiocin
    H Xu
    Pharmazeutische Biologie, Pharmazeutisches Institut, Eberhard Karls Universitat Tubingen, Auf der Morgenstelle 8, 72076 Tubingen, Germany
    Mol Genet Genomics 268:387-96. 2002
    ..spheroides was expressed in the couN3 (-) mutant. This led to the formation of bis-carbamoylated coumermycin D, a novel compound of the coumermycin series...
  9. doi request reprint novE and novG act as positive regulators of novobiocin biosynthesis
    Volker Dangel
    Pharmaceutical Biology, Pharmaceutical Institute, Eberhard Karls Universitat Tubingen, Auf der Morgenstelle 8, 72076 Tubingen, Germany
    Arch Microbiol 190:509-19. 2008
    ..RT-PCR experiments showed that expression of novG was detectable in the absence of NovE, and also that expression of novE occurred in absence of NovG...
  10. ncbi request reprint New aminocoumarin antibiotics from genetically engineered Streptomyces strains
    S M Li
    Pharmazeutische Biologie, Pharmazeutisches Institut, Eberhard Karls Universitat Tubingen, Auf der Morgenstelle 8, 72076 Tubingen, Germany
    Curr Med Chem 12:419-27. 2005
    ..Their inhibitory activity on gyrase in vitro as well as their antibacterial activity was determined. These results give further insight into the structure-activity relationships of aminocoumarins...
  11. pmc Antimicrobial and DNA gyrase-inhibitory activities of novel clorobiocin derivatives produced by mutasynthesis
    Ute Galm
    Pharmazeutische Biologie, Pharmazeutisches Institut, D 72076 Tuebingen, Germany
    Antimicrob Agents Chemother 48:1307-12. 2004
    ..Lack of a methyl group at O-4" of L-noviose resulted in an inactive compound. From these findings it appears that clorobiocin represents a "highly evolved" structure optimized for bacterial transport and DNA gyrase inhibition...
  12. ncbi request reprint Metabolic engineering of aminocoumarins: inactivation of the methyltransferase gene cloP and generation of new clorobiocin derivatives in a heterologous host
    Anja Freitag
    Pharmazeutische Biologie, Pharmazeutisches Institut, Eberhard Karls Universitat Tubingen, Auf der Morgenstelle 8, 72076 Tubingen, Germany
    Chembiochem 6:1411-8. 2005
    ..Attachment at 4-OH resulted in the highest antibacterial activity. This is the first time that an aminocoumarin antibiotic acylated at 4-OH in noviose has been detected...
  13. ncbi request reprint NovG, a DNA-binding protein acting as a positive regulator of novobiocin biosynthesis
    Alessandra S Eustáquio
    Pharmazeutische Biologie, Pharmazeutisches Institut, Eberhard Karls Universitat Tubingen, Auf der Morgenstelle 8, 72076 Tubingen, Germany
    Microbiology 151:1949-61. 2005
    ..The consensus sequence for the StrR and the putative NovG binding sites was GTTCRACTG(N)(11)CRGTYGAAC. Therefore, NovG and StrR apparently belong to the same family of DNA-binding regulatory proteins...
  14. doi request reprint Assembly and heterologous expression of the coumermycin A1 gene cluster and production of new derivatives by genetic engineering
    Manuel Wolpert
    Eberhard Karls Universitat Tubingen, Pharmazeutische Biologie, Auf der Morgenstelle 8, 72076 Tubingen, Germany
    Chembiochem 9:603-12. 2008
    ..The identities of the new compounds were verified by LC-MS, and their antibacterial activities were tested against Bacillus subtilis in an agar diffusion assay...
  15. ncbi request reprint Molecular cloning and sequence analysis of the clorobiocin biosynthetic gene cluster: new insights into the biosynthesis of aminocoumarin antibiotics
    Florence Pojer
    Eberhard Karls Universitat Tubingen, Pharmazeutische Biologie, Auf der Morgenstelle 8, D 72076 Tubingen, Germany
    Microbiology 148:3901-11. 2002
    ....
  16. pmc Identification of the novobiocin biosynthetic gene cluster of Streptomyces spheroides NCIB 11891
    M Steffensky
    Pharmazeutische Biologie, Pharmazeutisches Institut, Eberhard Karls Universitat Tubingen, 72076 Tubingen, Germany
    Antimicrob Agents Chemother 44:1214-22. 2000
    ..Heterologous expression of a key enzyme of novobiocin biosynthesis, i.e., novobiocic acid synthetase, in Streptomyces lividans TK24 further confirmed the involvement of the analyzed genes in the biosynthesis of the antibiotic...
  17. doi request reprint S-Adenosylmethionine (SAM) and antibiotic biosynthesis: effect of external addition of SAM and of overexpression of SAM biosynthesis genes on novobiocin production in Streptomyces
    Xin Qing Zhao
    Pharmaceutical Institute, Eberhard Karls Universitat Tubingen, Germany
    Arch Microbiol 192:289-97. 2010
    ....
  18. ncbi request reprint Methyltransferase genes in Streptomyces rishiriensis: new coumermycin derivatives from gene-inactivation experiments
    Shu Ming Li
    Eberhard Karls Universitat Tubingen, Pharmazeutische Biologie, Auf der Morgenstelle 8, Germany
    Microbiology 148:3317-26. 2002
    ..The new, demethylated secondary metabolites were produced in an amount at least as high as that of coumermycin A(1) in the wild-type...
  19. pmc Resistance genes of aminocoumarin producers: two type II topoisomerase genes confer resistance against coumermycin A1 and clorobiocin
    Elisabeth Schmutz
    Pharmazeutische Biologie, Eberhard Karls Universitat Tubingen, Germany
    Antimicrob Agents Chemother 47:869-77. 2003
    ..Expression of these genes in S. lividans TK24 resulted in moderate levels of resistance against novobiocin and coumermycin A(1), suggesting that these genes may be involved in antibiotic transport...
  20. ncbi request reprint Effects of deletions of mbtH-like genes on clorobiocin biosynthesis in Streptomyces coelicolor
    Manuel Wolpert
    Pharmaceutical Biology, Pharmaceutical Institute, Eberhard Karls Universitat Tubingen, Auf der Morgenstelle 8, 72076 Tubingen, Germany
    Microbiology 153:1413-23. 2007
    ....
  21. ncbi request reprint Clorobiocin biosynthesis in Streptomyces: identification of the halogenase and generation of structural analogs
    Alessandra S Eustáquio
    Pharmazeutische Biologie, Pharmazeutisches Institut, Eberhard Karls Universitat Tubingen, Auf der Morgenstelle 8, 72076 Tubingen, Germany
    Chem Biol 10:279-88. 2003
    ..Comparison of the antibacterial activity of clorobiocin analogs with -Cl, -H, or -CH(3) at C-8' showed that chlorine leads to 8-fold higher activity than hydrogen and to 2-fold higher activity than a methyl group...
  22. ncbi request reprint Mass spectrometric pathway monitoring of secondary metabolites: systematic analysis of culture extracts of Streptomyces species
    Bernd Kammerer
    Department of Clinical Pharmacology, Institute of Pharmacology and Toxicology, University Hospital Tubingen, 72076 Tubingen, Germany
    Anal Biochem 335:17-29. 2004
    ..Some new compounds were discovered, including bis-carbamoylated novobiocin, hydroxylated clorobiocin, and several structurally and not yet fully elucidated coumermycin derivatives or precursors...
  23. ncbi request reprint CloR, a bifunctional non-heme iron oxygenase involved in clorobiocin biosynthesis
    Florence Pojer
    Universitat Tubingen, Pharmazeutische Biologie, Auf der Morgenstelle 8, 72076 Tubingen, Germany
    J Biol Chem 278:30661-8. 2003
    ..The reaction catalyzed by CloR represents a new pathway for the formation of benzoic acids in nature...
  24. ncbi request reprint New aminocoumarin antibiotics from a cloQ-defective mutant of the clorobiocin producer Streptomyces roseochromogenes DS12.976
    Anja Freitag
    Pharmazeutische Biologie, Pharmazeutisches Institut, Eberhard Karls Universität Tübingen Auf der Morgenstelle 8, 72076 Tubingen, Germany
    J Antibiot (Tokyo) 57:205-9. 2004
    ..Declovanillobiocin lacks the chlorine atom at the aminocoumarin ring. All three compounds had lower antibiotic activity against Bacillus subtilis than clorobiocin...
  25. ncbi request reprint CloN6, a novel methyltransferase catalysing the methylation of the pyrrole-2-carboxyl moiety of clorobiocin
    Lucia Westrich
    Pharmazeutische Biologie, Pharmazeutisches Institut Eberhard Karls Universität Tübingen, Auf der Morgenstelle 8, 72076 Tubingen, Germany
    Chembiochem 4:768-73. 2003
    ....
  26. ncbi request reprint Metabolic engineering of the heterologous production of clorobiocin derivatives and elloramycin in Streptomyces coelicolor M512
    Anja Freitag
    Pharmazeutisches Institut, Eberhard Karls Universitat Tubingen, Germany
    Metab Eng 8:653-61. 2006
    ..Structural investigation of the resulting deoxysugars confirmed that both the endogeneous and the heterologous pathway involve a 3,5-epimerization of the deoxysugar, a hypothesis which had recently been questioned...
  27. pmc Aromatic prenylation in phenazine biosynthesis: dihydrophenazine-1-carboxylate dimethylallyltransferase from Streptomyces anulatus
    Orwah Saleh
    Pharmazeutische Biologie, Pharmazeutisches Institut, Eberhard Karls Universitat Tubingen, Auf der Morgenstelle 8, 72076 Tubingen, Germany
    J Biol Chem 284:14439-47. 2009
    ..The present finding extends the substrate range of this family, previously limited to phenolic compounds, to include also phenazine derivatives...
  28. ncbi request reprint Biosynthesis of the unusual 5,5-gem-dimethyl-deoxysugar noviose: investigation of the C-methyltransferase gene cloU
    Anja Freitag
    Pharmazeutische Biologie, Pharmazeutisches Institut, Eberhard Karls Universitat Tubingen, Auf der Morgenstelle 8, 72076 Tubingen, Germany
    Microbiology 152:2433-42. 2006
    ..Both compounds were isolated on a preparative scale, their structures were elucidated by 1H-NMR and mass spectroscopy and their antibacterial activity was assayed...
  29. ncbi request reprint Biosynthesis of clorobiocin: investigation of the transfer and methylation of the pyrrolyl-2-carboxyl moiety
    Christine Anderle
    Pharmazeutische Biologie, Pharmazeutisches Institut, Eberhard Karls Universitat Tubingen, Auf der Morgenstelle 8, 72076 Tubingen, Germany
    Arch Microbiol 187:227-37. 2007
    ..A mechanism for the methylation/acyl transfer process in the late steps of clorobiocin biosynthesis, involving CloN1, CloN2, CloN5, CloN6 and CloN7 is suggested...
  30. ncbi request reprint Improved mutasynthetic approaches for the production of modified aminocoumarin antibiotics
    Christine Anderle
    Pharmazeutische Biologie, Pharmazeutisches Institut, Eberhard Karls Universitat Tubingen, Auf der Morgenstelle 8, 72076 Tubingen, Germany
    Chem Biol 14:955-67. 2007
    ..Twenty-five aminocoumarin compounds were prepared by these methods, and their structures were elucidated with mass and 1H-NMR spectroscopy...
  31. doi request reprint Transcriptional regulation of the novobiocin biosynthetic gene cluster
    Volker Dangel
    Pharmaceutical Biology, Pharmaceutical Institute, Eberhard Karls Universitat Tubingen, Auf der Morgenstelle 8, 72076 Tubingen, Germany
    Microbiology 155:4025-35. 2009
    ..However, when the gyrase inhibitor novobiocin accumulates in the cultures, gyrB(R) is transcribed from its own promoter. Previous work has suggested that this promoter is controlled by the superhelical density of chromosomal DNA...
  32. pmc Biological activities of novel gyrase inhibitors of the aminocoumarin class
    Christine Anderle
    Pharmazeutische Biologie, Pharmazeutisches Institut, Universitat Tubingen, Auf der Morgenstelle 8, Tubingen D 72076, Germany
    Antimicrob Agents Chemother 52:1982-90. 2008
    ..Several compounds showed high levels of activity against staphylococci, including a methicillin-resistant Staphylococcus aureus strain. However, they showed only poor activities against gram-negative strains...
  33. ncbi request reprint Novobiocin biosynthesis: inactivation of the putative regulatory gene novE and heterologous expression of genes involved in aminocoumarin ring formation
    Alessandra S Eustáquio
    Pharmazeutische Biologie, Pharmazeutisches Institut, Eberhard Karls Universitat Tubingen, Auf der Morgenstelle 8, 72076 Tubingen, Germany
    Arch Microbiol 180:25-32. 2003
    ....
  34. ncbi request reprint CloN2, a novel acyltransferase involved in the attachment of the pyrrole-2-carboxyl moiety to the deoxysugar of clorobiocin
    Hui Xu
    Pharmazeutische Biologie, Pharmazeutisches Institut, Eberhard Karls Universitat Tubingen, 72076 Tubingen, Germany
    Microbiology 149:2183-91. 2003
    ..Furthermore, they indicate that the C-methylation at position 5 of the pyrrole moiety occurs after the attachment of pyrrole-2-carboxylic acid unit to the deoxysugar moiety...
  35. ncbi request reprint An unusual amide synthetase (CouL) from the coumermycin A1 biosynthetic gene cluster from Streptomyces rishiriensis DSM 40489
    Elisabeth Schmutz
    Eberhard Karls Universitat Tubingen, Pharmazeutische Biologie, Tubingen, Germany Institut für Pflanzenbiochemie, Halle Saale, Germany
    Eur J Biochem 270:4413-9. 2003
    ..In contrast, pyridine carboxylic acids were not accepted. 3-Dimethylallyl-4-hydroxybenzoic acid, the acyl component in novobiocin biosynthesis, was well accepted, despite its structural difference from the genuine acyl substrate of CouL...
  36. doi request reprint Reducing the variability of antibiotic production in Streptomyces by cultivation in 24-square deepwell plates
    Stefanie Siebenberg
    Pharmazeutische Biologie, Pharmazeutisches Institut, Eberhardt Karls Universitat Tubingen, Auf der Morgenstelle 8, 72076 Tubingen, Germany
    J Biosci Bioeng 109:230-4. 2010
    ....
  37. ncbi request reprint New aminocoumarin antibiotics derived from 4-hydroxycinnamic acid are formed after heterologous expression of a modified clorobiocin biosynthetic gene cluster
    Christine Anderle
    Pharmazeutisches Institut, Eberhard Karls Universitat Tubingen, Auf der Morgenstelle 8, 72076 Tubingen, Germany
    J Antibiot (Tokyo) 60:504-10. 2007
    ..The possible biosynthetic origin of these moieties is discussed...
  38. pmc A soluble, magnesium-independent prenyltransferase catalyzes reverse and regular C-prenylations and O-prenylations of aromatic substrates
    Yvonne Haagen
    Pharmazeutisches Institut, Eberhard Karls Universitat Tubingen, Auf der Morgenstelle 8, 72076 Tubingen, Germany
    FEBS Lett 581:2889-93. 2007
    ..e. an unusual "reverse" prenylation. With 1,3-dihydroxynaphthalene and 4-hydroxybenzoate as substrates Fnq26 catalyzes O-prenylations...
  39. doi request reprint Use of an inducible promoter for antibiotic production in a heterologous host
    Volker Dangel
    Pharmaceutical Biology, Pharmaceutical Institute, Eberhard Karls Universitat Tubingen, Auf der Morgenstelle 8, 72076 Tubingen, Germany
    Appl Microbiol Biotechnol 87:261-9. 2010
    ..Therefore, the tcp830 promoter presents a robust, easy-to-use system for the inducible expression of biosynthetic gene clusters in heterologous hosts, independent from the genuine regulatory network...
  40. ncbi request reprint A gene cluster for prenylated naphthoquinone and prenylated phenazine biosynthesis in Streptomyces cinnamonensis DSM 1042
    Yvonne Haagen
    Eberhard Karls Universitat Tubingen, Pharmazeutische Biologie, Auf der Morgenstelle 8, 72076 Tubingen, Germany
    Chembiochem 7:2016-27. 2006
    ..Two SAM-dependent methyltransferases are encoded within the cluster. Inactivation experiments showed that fnq9 is responsible for the 7-O-methylation and fnq27 for the 6-C-methylation reaction in FNQ I biosynthesis...
  41. ncbi request reprint New aminocoumarin antibiotics formed by a combined mutational and chemoenzymatic approach utilizing the carbamoyltransferase NovN
    Hui Xu
    Pharmazeutische Biologie, Pharmazeutisches Institut, Eberhard Karls Universitat Tubingen, Auf der Morgenstelle 8, 72076 Tuebingen, Germany
    Chem Biol 11:655-62. 2004
    ..The results give further insight into the structure-activity relationships of aminocoumarin antibiotics...
  42. ncbi request reprint In vitro and in vivo production of new aminocoumarins by a combined biochemical, genetic, and synthetic approach
    Ute Galm
    Pharmazeutische Biologie, Pharmazeutisches Institut, Eberhard Karls Universitat Tubingen, Auf der Morgenstelle 8, 72076 Tubingen, Germany
    Chem Biol 11:173-83. 2004
    ..This resulted in the formation of 32 new aminocoumarin compounds. The structures of these compounds were elucidated using FAB-MS and (1)H-NMR spectroscopy...
  43. ncbi request reprint Production of 8'-halogenated and 8'-unsubstituted novobiocin derivatives in genetically engineered streptomyces coelicolor strains
    Alessandra S Eustáquio
    Pharmazeutische Biologie, Pharmazeutisches Institut, Eberhard Karls Universität Tübingen Auf der Morgenstelle 8, 72076 Tubingen, Germany
    Chem Biol 11:1561-72. 2004
    ....
  44. ncbi request reprint Cloning and analysis of the simocyclinone biosynthetic gene cluster of Streptomyces antibioticus Tü 6040
    Ute Galm
    Pharmazeutische Biologie, Pharmazeutisches Institut, Auf der Morgenstelle 8, 72076 Tubingen, Germany
    Arch Microbiol 178:102-14. 2002
    ..Feeding of the mutant with the aminocoumarin moiety of novobiocin led to a new, artificial simocyclinone derivative...
  45. doi request reprint Prenyl transfer to aromatic substrates in the biosynthesis of aminocoumarins, meroterpenoids and phenazines: the ABBA prenyltransferase family
    Orwah Saleh
    Pharmazeutische Biologie, Pharmazeutisches Institut, Eberhard Karls Universitat Tubingen, Tubingen, Germany
    Phytochemistry 70:1728-38. 2009
    ..Therefore, the enzymes of this family represent attractive tools for the chemoenzymatic synthesis of bioactive molecules...
  46. ncbi request reprint Identification of a topoisomerase IV in actinobacteria: purification and characterization of ParYR and GyrBR from the coumermycin A1 producer Streptomyces rishiriensis DSM 40489
    Elisabeth Schmutz
    Eberhard Karls Universitat Tubingen, Pharmazeutische Biologie, Auf der Morgenstelle 8, D 72076 Tuebingen, Germany
    Microbiology 150:641-7. 2004
    ..This is believed to represent the first topo IV identified in the class of actinobacteria, and the first demonstration of the formation of a topo IV as a resistance mechanism of an antibiotic producer...
  47. ncbi request reprint Acyl transfer in clorobiocin biosynthesis: involvement of several proteins in the transfer of the pyrrole-2-carboxyl moiety to the deoxysugar
    Anja Freitag
    Pharmazeutische Biologie, Pharmazeutisches Institut, Eberhard Karls Universitat Tubingen, Auf der Morgenstelle 8, 72076 Tubingen, Germany
    Chembiochem 6:2316-25. 2005
    ..A possible mechanism for the role of these three proteins in the acyl-transfer process is suggested...
  48. pmc The structure of dimethylallyl tryptophan synthase reveals a common architecture of aromatic prenyltransferases in fungi and bacteria
    Ute Metzger
    Pharmazeutisches Institut, Universitat Tubingen, 72076 Tubingen, Germany
    Proc Natl Acad Sci U S A 106:14309-14. 2009
    ..These bacterial enzymes catalyze the prenylation of aromatic substrates in the biosynthesis of secondary metabolites (i.e., a reaction similar to that of DMATS)...
  49. ncbi request reprint Overexpression, purification and characterization of SimL, an amide synthetase involved in simocyclinone biosynthesis
    Thomas Luft
    Pharmazeutische Biologie, Pharmazeutisches Institut, Eberhard Karls Universitat Tubingen, Auf der Morgenstelle 8, 72076, Tubingen, Germany
    Arch Microbiol 183:277-85. 2005
    ..These findings make SimL a possible tool for the creation of new aminocoumarin antibiotics...
  50. pmc Heterologous expression of novobiocin and clorobiocin biosynthetic gene clusters
    Alessandra S Eustáquio
    Pharmazeutische Biologie, Pharmazeutisches Institut, Eberhard Karls Universitat Tubingen, Auf der Morgenstelle 8, 72076 Tubingen, Germany
    Appl Environ Microbiol 71:2452-9. 2005
    ..lividans TK24 derivatives were at least five times less productive. This method could also be used to carry out functional investigations. Shortening of the cosmids' inserts showed which genes are essential for antibiotic production...
  51. pmc A new group of aromatic prenyltransferases in fungi, catalyzing a 2,7-dihydroxynaphthalene 3-dimethylallyl-transferase reaction
    Elisa Haug-Schifferdecker
    Pharmazeutische Biologie, Pharmazeutisches Institut, Eberhard Karls Universitat Tubingen, 72076 Tubingen, Germany
    J Biol Chem 285:16487-94. 2010
    ..The genes for these fungal prenyltransferases are not located within recognizable secondary metabolic gene clusters. Their physiological function is yet unknown...
  52. ncbi request reprint The biosynthetic gene clusters of aminocoumarin antibiotics
    Shu Ming Li
    Pharmazeutische Biologie, Pharmazeutisches Institut, Eberhard Karls Universitat Tubingen, Tubingen, Germany
    Planta Med 72:1093-9. 2006
    ..However, detailed investigations of the biosynthesis revealed that the biosynthetic pathway and the enzymes involved are totally different from those identified in plants...
  53. ncbi request reprint Pharmacokinetic study of artemisinin after oral intake of a traditional preparation of Artemisia annua L. (annual wormwood)
    Karin Räth
    Pharmazeutische Biologie, Pharmazeutisches Institut, Universitat Tubingen, Tubingen, Germany
    Am J Trop Med Hyg 70:128-32. 2004
    ..Artemisinin plasma concentrations after intake of this herbal tea are sufficient for clinical effects, but insufficient to recommend such preparations as equivalent substitutes for modern artemisinin drugs in malaria therapy...
  54. ncbi request reprint High level expression of chorismate pyruvate-lyase (UbiC) and HMG-CoA reductase in hairy root cultures of Lithospermum erythrorhizon
    Annegret Köhle
    Pharmazeutische Biologie, Pharmazeutisches Institut, Eberhard Karls Universitat Tubingen, Auf der Morgenstelle 8, D 72076 Tubingen, Germany
    Plant Cell Physiol 43:894-902. 2002
    ..Shikonin accumulation remained unchanged even upon high expression of soluble HMGR...
  55. doi request reprint Aminocoumarins mutasynthesis, chemoenzymatic synthesis, and metabolic engineering
    Lutz Heide
    Pharmazeutische Biologie, Pharmazeutisches Institut, Universitat Tubingen, Tubingen, Germany
    Methods Enzymol 459:437-55. 2009
    ..These methods can be combined, allowing the generation of a wide variety of new compounds. This chapter may provide general pointers for the use of genetic methods in the generation of new antibiotics...
  56. doi request reprint Heterologous expression of the biosynthetic gene clusters of coumermycin A(1), clorobiocin and caprazamycins in genetically modified Streptomyces coelicolor strains
    Katrin Flinspach
    Pharmaceutical Biology, Pharmaceutical Institute, Eberhard Karls Universitat Tubingen, Auf der Morgenstelle 8, 72076 Tubingen, Germany
    Biopolymers 93:823-32. 2010
    ..6% Q2-5247 and 0.2 mg l(-1) CoCl(2)). In contrast, heterologous production of caprazamycin derivatives was optimal in strain M1154 (amounts of 152 mg l(-1) on average)...
  57. pmc Crystallization and preliminary X-ray analysis of the aromatic prenyltransferase CloQ from the clorobiocin biosynthetic cluster of Streptomyces roseochromogenes
    Sascha Keller
    Department of Biological Chemistry, John Innes Centre, Norwich NR4 7UH, England, UK
    Acta Crystallogr Sect F Struct Biol Cryst Commun 62:1153-5. 2006
    ..6%. CloQ is involved in the biosynthesis of the aminocoumarin antibiotic clorobiocin, which targets the essential bacterial enzyme DNA gyrase...
  58. pmc Structure-activity relationships of aminocoumarin-type gyrase and topoisomerase IV inhibitors obtained by combinatorial biosynthesis
    Ruth H Flatman
    Department of Biological Chemistry, John Innes Centre, Norwich Research Park, Colney, Norwich, NR4 7UH, United Kingdom
    Antimicrob Agents Chemother 50:1136-42. 2006
    ..This is the first report of a systematic evaluation of a series of aminocoumarins against both gyrase and topo IV. The results give further insight into the structure-activity relationships of aminocoumarin antibiotics...
  59. ncbi request reprint Functional characterizations of novWUS involved in novobiocin biosynthesis from Streptomyces spheroides
    Ta Thi Thu Thuy
    Institute of Biomolecule Reconstruction iBR, Department of Chemistry, Sun Moon University, 100, Kalsan ri, Tangjeong myeon, Asansi, Chungnam 336 708, Republic of Korea
    Arch Biochem Biophys 436:161-7. 2005
    ..NovS reduces the product formed from the reaction of NovW with dTDP-4-keto-6-deoxy-D-glucose in the presence of NADH to result in dTDP-l-rhamnose. Furthermore, a pathway for the biosynthesis of noviose is proposed...
  60. ncbi request reprint Assembly of dimeric variants of coumermycins by tandem action of the four biosynthetic enzymes CouL, CouM, CouP, and NovN
    Caren L Freel Meyers
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Biochemistry 43:15022-36. 2004
    ..Starting from alternative dicarboxy scaffolds, these four enzymes can be utilized in tandem to create additional variants of dimeric aminocoumarin antibiotics...
  61. doi request reprint Herba Artemisiae annuae tea preparation compared to sulfadoxine-pyrimethamine in the treatment of uncomplicated falciparum malaria in adults: a randomized double-blind clinical trial
    Christoph H Blanke
    Matyazo Health Centre, Diocese of Western Tanganyika, Kigoma, Tanzania
    Trop Doct 38:113-6. 2008
    ..After seven days, the cure rate was 7/10 for the Aa compared to 7/9 for SP; this dropped to 4/10 for Aa and 4/9 for SP at day 14 and to 1/9 for Aa and 3/8 for SP at day 28...
  62. pmc Simocyclinone D8, an inhibitor of DNA gyrase with a novel mode of action
    Ruth H Flatman
    Department of Biological Chemistry, John Innes Centre, Norwich Research Park, Colney, Norwich NR4 7UH, UK
    Antimicrob Agents Chemother 49:1093-100. 2005
    ..This is a novel mechanism for a gyrase inhibitor and presents new possibilities for antibacterial drug development...
  63. ncbi request reprint Characterization of NovP and NovN: completion of novobiocin biosynthesis by sequential tailoring of the noviosyl ring
    Caren L Freel Meyers
    Department of Biological Chemistry, and Molecular Pharmacology, LHRRB 309, Harvard Medical School, Boston, MA 02115, USA
    Angew Chem Int Ed Engl 43:67-70. 2004
  64. ncbi request reprint HPLC-MS/MS analysis of willow bark extracts contained in pharmaceutical preparations
    Bernd Kammerer
    Institute of Pharmacology and Toxicology, Department of Clinical Pharmacology, University Hospital Tubingen, Germany
    Phytochem Anal 16:470-8. 2005
    ..The described method may be utilised for the characterisation of herbal medicines in order to ensure comparability of medication in further clinical trials...
  65. ncbi request reprint Biosynthesis of the isoprenoid moieties of furanonaphthoquinone I and endophenazine A in Streptomyces cinnamonensis DSM 1042
    Gerhard Bringmann
    Institute of Organic Chemistry, University of Wurzburg, Am Hubland, D 97074 Wurzburg, Germany
    J Org Chem 72:4198-204. 2007
    ..The incorporation pattern of [2-13C]glycerol was consistent with a "reverse" prenyl transfer, that is, with the formation of a C-C bond from C-3 of GPP to the polyketide nucleus of FNQ I...
  66. ncbi request reprint Influence of willow bark extract on cyclooxygenase activity and on tumor necrosis factor alpha or interleukin 1 beta release in vitro and ex vivo
    Irmela Wagner
    Clin Pharmacol Ther 73:272-4. 2003
  67. ncbi request reprint Molecular replacement in the 'twilight zone': structure determination of the non-haem iron oxygenase NovR from Streptomyces spheroides through repeated density modification of a poor molecular-replacement solution
    Sascha Keller
    Department of Biological Chemistry, John Innes Centre, Norwich NR4 7UH, England
    Acta Crystallogr D Biol Crystallogr 62:1564-70. 2006
    ..It is predicted to perform two consecutive oxidative decarboxylation steps in the biosynthesis of the prenylated hydroxybenzoic acid moiety of the aminocoumarin antibiotic novobiocin...