Pharmaceutical Biology

Pharmaceutical Biotechnology and Antibiotic Discovery

  1. Leipoldt F, Zeyhle P, Kulik A, Kalinowski J, Heide L, Kaysser L (2015) Diversity of ABBA Prenyltransferases in Marine Streptomyces sp. CNQ-509: Promiscuous Enzymes for the Biosynthesis of Mixed Terpenoid Compounds. PLoS One 10: e0143237
  2. Rückert C, Leipoldt F, Zeyhle P, Fenical W, Jensen PR, Kalinowski J, Heide L, Kaysser L (2015) Complete genome sequence of Streptomyces sp. CNQ-509, a prolific producer of meroterpenoid chemistry. J Biotechnol 216: 140-141
  3. Zeyhle P, Bauer JS, Steimle M, Leipoldt F, Rösch M, Kalinowski J, Gross H, Heide L (2014) A membrane-bound prenyltransferase catalyzes the O-prenylation of 1,6-dihydroxyphenazine in the marine bacterium Streptomyces sp. CNQ-509. Chembiochem 15: 2385-2392
  4. Zeyhle P, Bauer JS, Kalinowski J, Shin-ya K, Gross H, Heide L (2014) Genome-based discovery of a novel membrane-bound 1,6-dihydroxyphenazine prenyltransferase from a marine actinomycete. PLoS One 9: e99122
  5. Zettler J, Xia H, Burkard N, Kulik A, Grond S, Heide L, Apel AK (2014) New aminocoumarins from the rare actinomycete Catenulispora acidiphila DSM 44928: identification, structure elucidation, and heterologous production. Chembiochem 15: 612-621
  6. Rückert C, Kalinowski J, Heide L, Apel AK (2014) Draft Genome Sequence of Streptomyces roseochromogenes subsp. oscitans DS 12.976, Producer of the Aminocoumarin Antibiotic Clorobiocin. Genome Announc 2: e01147-13
  7. Flinspach K, Rückert C, Kalinowski J, Heide L, Apel AK (2014) Draft Genome Sequence of Streptomyces niveus NCIMB 11891, Producer of the Aminocoumarin Antibiotic Novobiocin. Genome Announc 2: e01146-13
  8. Bonitz T, Zubeil F, Grond S, Heide L (2014) Unusual N-prenylation in diazepinomicin biosynthesis: the farnesylation of a benzodiazepine substrate is catalyzed by a new member of the ABBA prenyltransferase superfamily. PLoS One 8: e85707
  9. Jones AC, Gust B, Kulik A, Heide L, Buttner MJ, Bibb MJ (2013) Phage p1-derived artificial chromosomes facilitate heterologous expression of the FK506 gene cluster. PLoS One 8: e69319
  10. Novotna J, Gust B, Kulik A, Spizek J, Heide L (2013) Five gene products are required for assembly of the central pyrrole moiety of coumermycin A1. J Ind Microbiol Biotechnol 40: 915-925
  11. Boll B, Heide L (2013) A Domain of RubC1 of Rubradirin Biosynthesis Can Functionally Replace MbtH-Like Proteins in Tyrosine Adenylation. Chembiochem 14: 43-44
  12. Herbst DA, Boll B, Zocher G, Stehle T, Heide L (2013) Structural Basis of the Interaction of MbtH-Like Proteins, Putative Regulators of Non-Ribosomal Peptide Biosynthesis, with Adenylating Enzymes. J Biol Chem. 288: 1991-2003
  13. Zocher G, Saleh O, Heim JB, Herbst DA, Heide L, Stehle T. (2012) Structure-based engineering increased the catalytic turnover rate of a novel phenazine prenyltransferase. PLoS One 7 (10): e48427.
  14. Saleh O, Bonitz T, Flinspach K, Kulik A, Burkard N, Mühlenweg A, Vente A, Polnick S, Lämmerhofer M, Gust B, Fiedler HF, Heide L (2012) Activation of a silent phenazine biosynthetic gene cluster reveals a novel natural product and a new resistance mechanism against phenazines. MedChemComm 3: 1009-1019
  15. Saleh O, Flinspach K, Westrich L, Kulik A, Gust B, Fiedler HP, Heide L (2012) Mutational analysis of a phenazine biosynthetic gene cluster in Streptomyces anulatus 9663. Beilstein J Org Chem 8: 501-513
  16. Bonitz T, Alva V, Saleh O, Lupas AN, Heide L (2011) Evolutionary relationships of microbial aromatic prenyltransferases. PLoS One. 6(11):e27336.
  17. Siebenberg S, Burkard N, Knuplesch A, Gust B, Grond S, Heide L (2011) Two pathways for pyrrole formation in coumermycin A1 biosynthesis: the central pyrrole moiety is formed from L-threonine. Chembiochem 12: 2677-2685
  18. Boll B, Taubitz T, Heide L (2011) The role of MbtH-like proteins in the adenylation of tyrosine during aminocoumarin and vancomycin biosynthesis. J. Biol. Chem. 286: 36281-36290.
  19. Alt S, Mitchenall L, Maxwell A, Heide L: Inhibition of DNA gyrase and DNA topoisomerase IV of Staphylococcus aureus and Escherichia coli by aminocoumarin antibiotics (2011) J Antimicrob Chemother 66: 2061-2069
  20. Boll B, Hennig S, Xie C, Kyong Sohng J, Heide L (2011) Adenylate-forming enzymes of rubradirin biosynthesis: RubC1 is a bifunctional enzyme with aminocoumarin acyl ligase and tyrosine-activating domains. Chembiochem 12: 1105 – 1114
  21. Alt S, Burkard N, Kulik A, Grond S, Heide L (2011) An artificial pathway to 3,4-dihydroxybenzoic acid allows generation of a new aminocoumarin antibiotic recognized by catechol transporters of E. coli. Chem Biol 18: 304-313
  22. Siebenberg S, Kaysser L, Wemakor E, Heide L, Gust B, Kammerer B (2011) Identification and structural elucidation of new caprazamycins from Streptomyces sp. MK730-62F2 by liquid chromatography/electrospray ionization tandem mass spectrometry. Rapid Commun Mass Spectrom. 25: 495-502
  23. Seeger K, Flinspach K, Haug-Schifferdecker E, Kulik A, Gust B, Fiedler HP, Heide L (2010) The biosynthetic genes for prenylated phenazines are located at two different chromosomal loci of Streptomyces cinnamonensis DSM 1042. Microb Biotechnol 4:252-62
  24. Metzger U, Keller S, Stevenson CE, Heide L, Lawson DM (2010) Structure and mechanism of the magnesium-independent aromatic prenyltransferase CloQ from the clorobiocin biosynthetic pathway. J Mol Biol 404: 611-626
  25. Flinspach K, Westrich L, Kaysser L, Siebenberg S, Gomez- Escribano JP, Bibb M, Gust B, Heide L (2010) Heterologous expression of the biosynthetic gene clusters of coumermycin A1, clorobiocin and caprazamycins in genetically modified Streptomyces coelicolor strains. Biopolymers 93: 823-832
  26. Haug-Schifferdecker E, Arican D, Brückner R, Heide L (2010) A new group of aromatic prenyltransferases in fungi, catalysing a 2,7-dihydroxynaphthalene 3-dimethylallyl- transferase reaction. J Biol Chem 285: 16487-16494
  27. Zhao X, GustB, Heide L (2010) S-Adenosylmethionine (SAM) and antibiotic biosynthesis: Effect of external addition of SAM and of overexpression of SAM biosynthesis genes on novobiocin production in Streptomyces. Arch Microbiol 192:289–297
  28. Dangel V, Westrich L, Smith MCM, Heide L, Gust B (2010) Use of an inducible promoter for antibiotic production in a heterologous host. Appl Microbiol Biotechnol 87: 261-269
  29. Siebenberg S, Bapat PM, Lantz AE, Gust B, Heide L (2010) Reducing the variability of antibiotic production in Streptomyces by cultivation in 24-square deepwell plates. J Biosci Bioeng 109: 230-234
  30. Mavrodi DV, Tobin L. Peever TL, Mavrodi OV, Parejko JA, Raaijmakers JM, Lemanceau P, Mazurier S, Heide L, Blankenfeldt W, Weller DM, Thomashow LS (2010) Diversity and evolution of the phenazine biosynthesis pathway. Appl Env Microbiol, 76:866-879
  31. Dangel V, Härle J, Goerke C, Wolz C, Gust B, Pernodet JL, Heide L (2009) Transcriptional regulation of the novobiocin biosynthetic gene cluster. Microbiology 155: 4025-4035
  32. Metzger U, Schall C, Zocher G, Unsöld I, Stec E, Li SM, Heide L, Stehle T (2009) The structure of dimethylallyl tryptophan synthase reveals a common architecture of aromatic prenyltransferases in fungi and bacteria. Proc Nat Acad Sci (USA) 106:14309-14314
  33. Saleh O, Gust B, Boll B, Fiedler HP, Heide L (2009) Aromatic prenylation in phenazine biosynthesis: dihydrophenazine-1-carboxylate dimethylallyltransferase from Streptomyces anulatus. J Biol Chem 284:14439-14447
  34. Dangel V, Eustáquio AS, Gust B, Heide L (2008) novE and novG act as positive regulators of novobiocin biosynthesis. Arch. Microbiol. 190: 509-519.
  35. Heide L, Westrich L, Anderle C, Gust B, Kammerer B, Piel J (2008) Use of a halogenase of hormaomycin biosynthesis for formation of new clorobiocin analogs with 5-chloro-pyrrole moieties. ChemBioChem 9:1992-1999.
  36. Anderle C, Stieger M, Burrell M, Reinelt S, Maxwell A, Page M, Heide L (2008) Biological activities of novel gyrase inhibitors of the aminocoumarin class. Antimicrob Agents Chemother 52: 1982–1990.
  37. Wolpert M, Heide L, Kammerer B, Gust B (2008) Assembly and heterologous expression of the coumermycin A1 gene cluster and production of new derivatives by genetic engineering. ChemBioChem 9: 603-612.
  38. Anderle C, Li S-M, Kammerer B, Gust B, Heide L (2007) New aminocoumarin antibiotics derived from 4-hydroxycinnamic acid are formed after heterologous expression of a modified clorobiocin biosynthetic gene cluster. J Antibiot (Tokyo). 60: 504-510.
  39. Anderle C, Hennig S, Kammerer B, Li S-M, Wessjohann L, Gust B, Heide L (2007) Improved mutasynthetic approaches for the production of modified aminocoumarin antibiotics. Chem & Biol 14: 955–967
  40. Haagen Y, Unsöld I, Westrich L, Gust B, Heide L (2007) A soluble, magnesium-independent prenyltransferase catalyzes reverse and regular C-prenylations and O-prenylations of aromatic substrates. FEBS Letters 581: 2889-2893
  41. Bringmann G, Haagen Y, Gulder TAM, Gulder T, Heide L (2007) Biosynthesis of the isoprenoid moieties of furanonaphthoquinone I and endophenazine A in Streptomyces cinnamonensis DSM 1042. J Org Chem 72: 4198-4204.
  42. Anderle C, Alt A, Gulder T, Bringmann G, Kammerer B, Gust B and Heide L (2007) Biosynthesis of clorobiocin: Investigation of the transfer and methylation of the pyrrolyl-2-carboxyl moiety. Arch Microbiol 187, 227-237.
  43. Wolpert M, Gust B, Kammerer B, Heide L (2007) Effects of deletions of mbtH-like genes on clorobiocin biosynthesis in Streptomyces coelicolor. Microbiology 153: 1413-1423
  44. Haagen Y, Glück K, Fay K, Kammerer B, Gust B, Heide L (2006) A gene cluster for prenylated naphthoquinone and prenylated phenazine biosynthesis in Streptomyces cinnamonensis DSM 1042. Chembiochem 7: 2016-2027
  45. Keller S, Pojer F, Heide L, Lawson DM (2006) Molecular replacement in the "twilight zone": crystal structure determination of the non-heme iron oxygenase NovR from Streptomyces spheroides through repeated density modification of a poor molecular replacement solution. Acta Cryst D 62:1564-1570
  46. Keller S, Pojer F, Heide L, Lawson DM (2006) Crystallization and preliminary X-ray analysis of the aromatic prenyltransferase CloQ from the clorobiocin biosynthetic cluster of Streptomyces roseochromogenes. Acta Cryst. F 62, 1153–1155
  47. Freitag, A., Méndez, C., Salas, J.A., Kammerer, B., Li, S.-M., Heide, L (2006). Metabolic engineering of the heterologous production of clorobiocin derivatives and elloramycin in Streptomyces coelicolor M512. Metab Eng 8: 653-661
  48. Freitag A, Li S-M, Heide L (2006) Biosynthesis of the unusual 5,5-gem-dimethyl-deoxysugar noviose: investigation of the C-methyltransferase gene cloU. Microbiology 152: 2433-2442
  49. Flatman RH, Eustaquio A, Li S-M, Heide L, Maxwell A (2006) Structure-activity relationships of aminocoumarin-type gyrase and topoisomerase iv inhibitors obtained by combinatorial biosynthesis. Antimicrob Agents Chemother 50: 1136–1142
  50. Kammerer B, Kahlich R, Biegert C, Gleiter CH, Heide L (2005) HPLC-MS/MS analysis of willow bark extracts contained in pharmaceutical preparations. Phytochem Anal 16: 470-478
  51. Freitag A, Wemakor E, Li S-M, Heide L (2005) Acyl transfer in clorobiocin biosynthesis: Involvement of several proteins in the transfer of the pyrrole-2-carboxyl moiety to the deoxysugar. ChemBioChem 6: 2316-2325
  52. Luft T, Li S-M, Scheible H, Kammerer B, Heide L (2005) Overexpression, purification and characterization of SimL, an amide synthetase involved in simocyclinone biosynthesis. Arch Microbiol 183: 277-285
  53. Eustáquio AS, Li S-M, Heide L (2005) NovG, a DNA-binding protein acting as a positive regulator of novobiocin biosynthesis. Microbiology 151: 1949-1961.
  54. Freitag A, Rapp H, Heide L, Li S-M (2005) Metabolic engineering of aminocoumarins: Inactivation of the methyltransferase gene cloP and generation of new clorobiocin derivatives in a heterologous host. ChemBioChem 6: 1411-1418
  55. Eustáquio AS, Gust B, Galm U, Li S-M, Chater KF, Heide L (2005) Heterologous expression of the biosynthetic gene clusters of novobiocin and clorobiocin. Appl Environ Microbiol 71: 2452-2459
  56. Thuy TTT, Lee HC, Kim C-G, Heide L, Sohng JK (2005) Functional characterizations of novWUS involved in novobiocin biosynthesis from Streptomyces spheroides. Arch Biochem Biophys 436: 161-176
  57. Flatman RH, Howells AJ, Heide L, Fiedler H-P, Maxwell A (2005) Simocyclinone D8: an inhibitor of DNA gyrase with a novel mode of action. Antimicrob Agents Chemother 49: 1093-1100
  58. Freel Meyers CL, Oberthür M, Heide L, Kahne D, Walsh CT (2004) Assembly of dimeric variants of coumermycins by tandem action of the four biosynthetic enzymes CouL, CouM, CouP, and NovN. Biochemistry 43: 15022-15036
  59. Eustáquio AS, Gust B, Li S-M, Pelzer S, Wohlleben W, Chater KF, Heide L (2004) Production of 8´-halogenated and 8´-unsubstituted novobiocin derivatives in genetically engineered Streptomyces coelicolor strains. Chem & Biol 11: 1561-1572.
  60. Kammerer B, Kahlich R, Laufer S, Li SM, Heide L, Gleiter CH (2004) Mass spectrometric pathway monitoring of secondary metabolites - Systematic analysis of culture extracts of Streptomyces species. Anal Biochem 335, 17-29
  61. Biegert C, Wagner I, Lüdtke R, Kötter I, Lohmüller C, Günaydin I, Taxis K, Heide L (2004) Efficacy and safety of willow bark extract in the treatment of osteoarthritis and rheumatoid arthritis. Results of two randomized double-blind controlled trials. J Rheumatol 31, 2121-2130
  62. Xu H, Heide L, Li S-M (2004) New aminocoumarin antibiotics formed by a combined mutational and chemoenzymatic approach utilizing the carbamoyltransferase NovN. Chem & Biol 11: 655-662
  63. Freitag A, Galm U, Li S.-M, Heide L (2004). New aminocoumarin antibiotics from a cloQ-defective mutant of the clorobiocin producer Streptomyces roseochromogenes DS12.976. J Antibiotics 57: 205-210
  64. Galm U, Heller S, Shapiro S, Page M, Li S-M, Heide L (2004) Antimicrobial and DNA gyrase-inhibitory activities of novel clorobiocin derivatives prepared by mutasynthesis. Antimicrob Agents Chemother. 48: 1307-1312
  65. Galm U, Dessoy MA, Schmidt J, Wessjohann LA, Heide L (2004) In vitro and in vivo production of new aminocoumarins by a combined biochemical, genetic and synthetic approach. Chem & Biol 11: 173-183
  66. Schmutz E, Hennig S, Li S-M, Heide L (2004) Identification of a topoisomerase IV in actinobacteria: purification and characterization of ParYR and GyrBR from the coumermycin A1 producer Streptomyces rishiriensis DSM 40489. Microbiology 150: 641-647
  67. Freel Meyers CL, Oberthür M, Xu H, Heide L, Kahne D, Walsh CT (2004) Characterization of NovP and NovN: Completion of novobiocin biosynthesis by sequential tailoring of the noviosyl ring. Angew Chem Int Ed Engl, 43: 67-70.
  68. Schmutz E, Steffensky M, Schmidt J, Porzel A, Li S-M, Heide L (2003) An unusual amide synthetase (CouL) from the coumermycin A1 biosynthetic gene cluster from Streptomyces rishiriensis DSM 40489. Eur J Biochem 270: 4413-4419
  69. Pojer F, Kahlich R, Kammerer K, Li S-M, Heide L (2003) CloR, a bifunctional non-heme iron oxygenase involved in clorobiocin biosynthesis. J Biol Chem 278:30661-30668.
  70. Westrich L, Heide L, Li S-M (2003) CloN6, a novel methyltransferase catalysing the methylation of the pyrrole-2-carboxyl moiety of clorobiocin. ChemBiochem 4: 100-106.
  71. Xu H, Kahlich R, Kammerer B, Heide L, Li S-M (2003) CloN2, a novel acyltransferase involved in the attachment of the pyrrole-2-carboxyl moiety to the deoxysugar of clorobiocin. Microbiology 149: 2183-2191
  72. Eustáquio A, Luft T, Wang Z-X, Gust B, Chater KF, Li S-M, Heide L (2003) Novobiocin biosynthesis: inactivation of the putative regulatory gene novE and heterologous expression of genes involved in aminocoumarin ring formation. Arch. Microbiol. 180: 25-32
  73. Eustáquio A, Gust B, Luft T, Li S-M, Chater K, Heide L (2003) Clorobiocin biosynthesis in Streptomyces: Identification of the halogenase and generation of structural analogues. Chem. & Biol. 10: 279-88.
  74. Wagner I, Heide L (2003) Effects of willow bark extract (Letter). Clin. Pharmacol. Ther. 74: 96-97
  75. Wagner I, Greim C, Laufer S, Heide L, Gleiter CH (2003) Influence of willow bark extract on cyclooxygenase activity and on tumor necrosis factor α or interleukin 1ß release in vitro and ex vivo. Clin. Pharmacol. Ther. 73: 272-274
  76. Pojer F, Wemakor E, Kammerer B, Chen H, Walsh CT, Li S-M, Heide L (2003) CloQ, a prenyltransferase involved in clorobiocin biosynthesis. Proc. Natl. Acad. Sci. (USA) 100: 2316-2321
  77. Schmutz E, Mühlenweg A, Li S-M, Heide L (2003) Resistance genes of aminocoumarin producers: Two type II topoisomerase genes confer resistance against coumermycin A1 and clorobiocin. Antimicrob. Agents Chemother. 47: 869-877
  78. Köhle A, Sommer S, Li S-M, Schilde-Rentschler L, Ninnemann H, Heide L (2003) Secondary metabolites in transgenic tobacco and potato: high accumulation of 4-hydroxybenzoic acid glucosides result from high expression of the bacterial gene ubiC. Molecular Breeding 11:15-24
  79. Wagner I, Heide L (2003) Salicin and treatment of rheumatic diseases (Letter). J Rheumatol 30, 1125
  80. Xu H, Wang Z-X, Schmidt J, Heide L, Li S-M (2002) Genetic analysis of the biosynthesis of the pyrrole and carbamoyl moieties of coumermycin A1 and novobiocin. Mol. Genet. Genomics 268: 387-396
  81. Li S-M, Westrich L, Schmidt J, Kuhnt C, Heide L (2002) Methyltransferase genes in Streptomyces rishiriensis: new coumermycin derivatives from gene-inactivation experiments. Microbiology 148: 3317-3326
  82. Pojer F, Li S-M, Heide L (2002) Identification of the clorobiocin biosynthetic gene cluster. New insights into the biosynthesis of aminocoumarin antibiotics. Microbiology 148: 3901-3911
  83. Köhle A, Sommer S, Yazaki K, Ferrer A, Boronat A, Li S-M, Heide L (2002) High level expression of chorismate pyruvate-lyase (UbiC) and HMG-CoA reductase in hairy root cultures of Lithospermum erythrorhizon. Plant & Cell Phys. 43: 894-902
  84. Galm U, Schimana J, Fiedler H-P, Schmidt J, Li S-M, Heide L (2002) Cloning and analysis of the simocyclinone biosynthetic gene cluster of Streptomyces antibioticus Tü 6040. Arch Microbiol, 178: 102-114
  85. Schmid B, Kötter I, Heide L (2001) Pharmacokinetics of salicin after oral application of a standardized willow bark extract. Eur. J. Clin. Pharmacol. 57, 387-391.
  86. Deutsche Fassung: Schmid B, Biegert C, Kötter I, Heide L (2002) Pharmakokinetik von Salicin nach oraler Gabe eines standardisierten Weidenrindenextraktes. In: Phytopharmaka VII (Schultz V, Rietbrock N, Roots I, Loew D, Eds), Steinkopf, Darmstadt, Germany. pp. 93-100.
  87. Li S-M, Wemakor E, Heide L (2001) PCR amplification of 1-deoxy-D-xylulose 5-phosphate synthase (dxs) genes from different Streptomyces species: Evidence for the existence of two dxs gene families. Molecular Biology Today 2: 61-66
  88. Schmid B, Lüdtke R, Selbmann H-K, Schaffner W, Kötter I, Tschirdewahn B, Heide L (2001) Efficacy and tolerability of a standardized willow bark extract in patients with osteoarthritis: randomized placebo-controlled, double blind clinical trial; Phytother. Res. 15, 1-7
  89. Wang Z-X, Li S-M, Heide L (2000) Identification of the coumermycin A1 biosynthetic gene cluster of Streptomyces rishiriensis DSM 40489; Antimicrob. Agents Chemother. 44, 3040-3048
  90. Steffensky M, Li S-M, Heide L (2000) Cloning, overexpression and purification of novobiocic acic synthetase from Streptomyces spheroides NCIB 11891; J. Biol. Chem. 275, 21754-21760
  91. Steffensky M, Mühlenweg A, Wang Z-X, Wemakor E, Li S-M, Heide L (2000) Molecular cloning of the novobiocin biosynthetic gene cluster of Streptomyces spheroides NCIB 11891. Antimicrob. Agents Chemother. 44, 1214-1222
  92. Boehm R, Sommer S, Li S-M, Heide L (2000) Genetic engineering of shikonin biosynthesis: Expression of the bacterial ubiA gene in Lithospermum erythrorhizon. Plant & Cell Physiol. 41: 911-919
  93. Boehm R, Sommer S, Severin K, Li S-M, Heide L (2000) Active expression of the ubiA Gene from E.coli in tobacco: Influence of plant ER-specific signal peptides on the expression of a membrane-bound prenyltransferase in plant cells. Transgenic Res. 9: 477-486
  94. Yamamoto H, Inoue K, Li S-M, Heide L (2000) Geranylhydroquinone 3’’-hydroxylase, a cytochrome P-450 monooxygenase from Lithospermum erythrorhizon cell suspension cultures. Planta, 210:312-317
  95. Schmid B, Lüdtke R, Selbmann H-K, Schaffner W, Kötter I, Tschirdewahn B, Heide L (2000) Wirksamkeit und Verträglichkeit eines standardisierten Weidenrindenextraktes bei Arthrose-Patienten: Randomisierte, placebo-kontrollierte Doppelblindstudie; Z. Rheumatol. 59: 314-320
  96. Sommer S, Köhle A,Yazaki K, Shimomura K, Bechthold A, Heide L (1999) Genetic engineering of shikonin biosynthesis. Hairy root cultures of Lithospermum erythrorhizon transformed with the bacterial ubiC gene. Plant Mol. Biol. 39: 683-693
  97. Mühlenweg A, Melzer M, Li S-M, Heide L (1998) 4-Hydroxybenzoate 3-geranyltransferase from Lithospermum erythrorhizon. Purification of a plant membrane-bound prenyltransferase. Planta 205: 407-413
  98. Lange BM, Severin K, Bechthold A, Heide L (1998) Regulatory role of microsomal 3-hydroxy-3-methylglutaryl-coenzyme A reductase for shikonin biosynthesis in Lithospermum erythrorhizon cell suspension cultures. Planta 204: 234-241
  99. Li S-M, Hennig S, Heide L (1998) Shikonin: a geranyl diphosphate-derived plant hemiterpenoid formed via the mevalonate pathway. Tetrahedron Letters 39: 2721-2724
  100. Li S-M, Hennig S, Heide L (1998) Biosynthesis of the dimethylallyl moiety of novobiocin via a non-mevalonate pathway. Tetrahedron Letters 39: 2717-2720
  101. Steffensky M, Li S-M, Vogler B, Heide L (1998) Novobiocin biosynthesis in Streptomyces spheroides: Identification of a dimethylallyl diphosphate : 4-hydroxyphenylpyruvate dimethylallyl transferase. FEMS Microbiol. Lett. 161: 69-74
  102. Sommer S, Siebert M, Bechthold A, Heide L (1998) Specific induction of secondary product formation in transgenic plant cell cultures using an inducible promotor. Plant Cell Rep 17: 891-896
  103. Li S-M, Bechthold A, Heide L (1998) Sequence announcement AF053721: Putative retrotransposon polyprotein from Lithospermum erythrorhizon. Plant Mol. Biol. 38: 505
  104. Sommer S, Heide L (1998) Expression of bacterial chorismate pyruvate-lyase in tobacco: Evidence for the presence of chorismate in the plant cytosol. Plant & Cell Physiol. 39: 1240-1244
  105. Li S-M, Wang Z-X, E. Wemakor, Heide L (1997) Metabolization of the artificial secondary metabolite 4-hydroxybenzoate in ubiC-transformed tobacco. Plant & Cell Physiology 38, 844-850
  106. Brühl A, Schmid B, Feser H, Heide L (1997) Laienverständnis pflanzlicher und synthetischer Arzneimittel. Ergebnisse einer repräsentativen Befragung. Pharmazeut. Ztg. 31: 11-19
  107. Yazaki K, Kataoka M, Honda G, Severin K, Heide L (1997) cDNA Cloning and gene expression of phenylalanin ammonia-lyase in Lithospermum erythrorhizon. Biosci. Biotech. Biochem. 61, 1995-2003
  108. Boehm R, Li S-M, Melzer M, Heide L (1997) 4-Hydroxybenzoate prenyltransferases in cell-free extracts of Lithospermum erythrorhizon cell cultures. Phytochemistry 44, 419-424
  109. Li S-M, Wang Z-X, Heide L (1997) Purification of UDP-glucose:4-hydroxybenzoate glucosyltransferase from cell cultures of Lithospermum erythrorhizon. Phytochemistry 46: 27-32
  110. Wang Z-X, Li S-M, Löscher R, Heide L (1997) 4-Coumaroyl coenzyme A 3-hydroxylase activity from cell cultures of Lithospermum erythrorhizon and its relationship to polyphenol oxidase. Arch. Biochem. Biophys. 347: 249-255
  111. Gaisser S, Heide L (1996) Inhibiton and regulation of shikonin biosynthesis in suspension cultures of Lithospermum. Phytochemistry 41, 1065-1072
  112. Li S-M, Wang Z-X, Heide L (1996) Purification and characterization of an alcohol dehydrogenase from Lithospermum erythrorhizon cell cultures. Plant Cell Rep. 15, 786-790
  113. Siebert M, Sommer S, Li S-M, Wang Z-X, Severin K, Heide L (1996) Genetic engineering of plant secondary metabolism. Accumuation of 4-hydroxybenzoate glucosides as a result of the expression of the bacterial ubiC gene in tobacco. Plant Physiol. 112, 811-819
  114. Sommer S, Severin K, Camara B, Heide L (1995) Intracelluar localization of geranylpyrophosphate synthase from cell cultures of Lithospermum erythrorhizon. Phytochemistry 38, 623-627
  115. Melzer M, Heide L (1994) Characterization of polyprenyldiphosphate:4-hydroxybenzoate polyprenyltransferase from Escherichia coli. Biochim. Biophys. Acta 1212, 93-102
  116. Siebert M, Severin K, Heide L (1994) Formation of 4-hydroxybenzoate in Escherichia coli: characterization of the ubiC gene and its encoded enzyme chorismate pyruvate-lyase. Microbiology 140, 897-904
  117. Löscher R, Heide L (1994) Biosynthesis of p-hydroxybenzoate from p-coumarate and p-coumaroyl-coenzyme A in cell-free extracts of Lithospermum erythrorhizon cell cultures. Plant Physiol. 106, 271-279
  118. Schaaf PM, Heide L, Leistner E, Tani Y, El-Olemy MM (1993) Immobilization of isochorismate hydroxymutase. Comparison of native versus immobilized enzyme. J. Nat. Prod. 56: 1304-1312
  119. Heide L, Melzer M, Siebert M, Bechthold A, Schröder J, Severin K (1993) Clarification of the Escherichia coli genetic map in the 92-minute region containing the ubiCA operon and the plsB, dgk, lexA, and dinF genes. J Bacteriol. 175: 5728-5729.
  120. Cho H, Heide L, Floss HG (1992) Synthesis of D-(-)-[1,7-13C2]shikimic acid. J. Labell. Comp. Radiopharm. XXXI, 589-594
  121. Siebert M, Bechthold A, Melzer M, May U, Berger U, Schröder G, Schröder J, Severin K, Heide L (1992) Ubiquinone biosynthesis. Cloning of the genes coding for chorismate pyruvate-lyase and 4-hydroxybenzoate octaprenyl transferase from Escherichia coli. FEBS Letters 307, 347-350
  122. Bechthold A, Berger U, Heide L (1991) Parthial purification, properties and kinetic studies of UDP-Glucose:p‑hydr­oxybenzoate glucosyl transferase from cell cultures of Lithospermum erythrorhizon. Arch. Biochem. Biophys. 288, 39-47
  123. Yazaki K, Heide L, Tabata M (1991) Formation of p-hydroxybenzoic acid from p-coumaric acid by cell free extracts of Lithospermum erythrorhizon cell cultures. Phytochemistry 30, 2233-2236
  124. Heide L (1991) Enzymatic synthesis of labelled geraniol. J. Labell. Comp. Radiopharm. XXIX, 1261-1262
  125. Heide L, Tabata M (1989) Facile enzymatic synthesis of labelled geranylpyro­phosphate. Tetrahedron Letters 30, 813‑814
  126. Heide L, Floss HG, Tabata M (1989) Incorporation of shikimic acid into p‑hydroxybenzoic acid in Lithospermum erythrorhizon cell cultures. Phytochemistry 28, 2643‑2645
  127. Heide L, Nishioka N, Fukui H, Tabata M (1989) Enzymatic regulation of shikonin biosynthesis in Lithospermum erythrorhizon cell cultures. Phytochemistry 28, 1873‑1877
  128. Heide L, Berger U (1989) Partial purification and properties of geranylpyro­phosphate synthase from Lithospermum erythrorhizon cell cultures. Arch. Biochem. Biophys. 273, 331‑338
  129. Heide L (1988) Geranylpyrophosphate synthase from cell cultures of Lithospermum erythrorhizon. FEBS Letters 237, 159‑162
  130. Heide L, Tabata M (1987) Enzyme activities in cell‑free extracts of shiko­nin‑producing Lithospermum erythrorhizon cell suspension cultures. Phytochemistry 26, 1645‑1650
  131. Heide L, Tabata M (1987) Geranylpyrophosphate: p‑hydroxybenzoate geranyl­transferase activity in extracts of Lithospermum erythrorhizon cell cultures. Phytochemistry 26, 1651‑1655
  132. Heide L, Leistner E (1983) Enzyme activities in extracts of anthra­quinone‑con­taining cells of Galium mollugo L. Phytochemistry 22, 659‑662
  133. Heide L, Leistner E (1982) Versuche zur Synthese natürlich vorkommender prenylierter Naphthalinderivate. Nachweis eines neuen Prenylnaphthochi­nonderivates in Galium mollugo. Z. Naturforsch. 37c, 354‑362
  134. Heide L, Arendt S, Leistner E (1982) Enzymatic synthesis, characteri­za­tion, and metabolism of the coenzyme A ester of o‑succinylbenzoic acid, an intermediate in menaquinone (vitamin K2) biosynthesis. J. Biol. Chem. 257, 7396‑7400
  135. Heide L, Kolkmann R, Arendt S, Leistner E (1982) Enzymic synthesis of o‑succinylbenzoyl‑CoA in cell free extracts of anthraquinone producing Galium mollugo L. cell suspension cultures. Plant Cell Rep. 1, 180‑182
  136. Heide L, Leistner E (1981) Enzymatic synthesis of the coenzyme A ester of o‑succinylbenzoic acid, an intermediate in menaquinone (vitamin K2) biosynthesis. FEBS Letters 128, 201‑204
  137. Heide L, Leistner E (1981) 2‑Methoxycarbonyl‑3‑prenyl‑1,4‑ naphtho­quinone, a metabolite related to the biosynthesis of mollugin and anthraquinones in Galium mollugo L. J. Chem. Soc. Chem. Comm. 1981, 334‑ 336