Jurgen Rohr

Contact Information

363 BioPharm Complex
789 South Limestone Street
Lexington, KY 40536-0596

Phone: 859-323-5031
Fax: 859-257-7564

Contact by email

Positions

  • Director, Division of Drug Discovery
    Department of Pharmaceutical Sciences
  • Professor
    Department of Pharmaceutical Sciences

Education

  • B.S. in Chemistry
    Studium of Chemistry and Biochemistry, in Göttingen, Germany, 1979
  • M.S. in Organic Chemistry
    Studium of Chemistry and Biochemistry, in Göttingen, Germany and Columbus, Ohio, 1981
  • Ph.D. in Bioorganic Chemistry and Microbiology
    University of Göttingen, Germany , 1984
  • Postdoctoral Research in Biochemistry
    Ohio State University, 1986-1987

Jurgen Rohr, Ph.D.

Dr. Rohr's research is focused on natural product drugs, i.e. antibiotics, anticancer drugs and drugs against bone diseases. It includes the elucidation of complex multi-step biosynthetic pathways, carried out by bacteria, fungi or plants, with particular emphasis on enzyme mechanisms. The results of these biosynthetic studies are used to generate modified natural product drugs through genetic engineering (pathway engineering, combinatorial biosynthesis).

Used techniques in the Rohr-laboratory include isolation and structure elucidation of natural products, incorporation experiments with isotope-labeled biosynthetic precursors, NMR spectroscopy, mass spectrometry, and recombinant DNA techniques for the targeted interruption or recombination of genes of the biosynthetic pathways. Newer aspects of the research include (i) the testing of antitumor drugs using human cancer cell lines, (ii) the investigation of biochemical signal-transduction pathways influenced by anticancer drugs, and (iii) novel cancer gene therapy concepts. Dr. Rohr's publications (ca. 120) can be found in biochemical and chemical journals, such as Angew. Chem., Biochemistry, Chem. Biol., ChemBioChem, Chem. Commun., Gene, J. Am. Chem. Soc., J. Bacteriol., J. Biol. Chem., J. Nat. Prod., J. Org. Chem., Microbiol., Mol. Gen. Genet., Nat. Prod. Rep. etc.

Before joining University of Kentucky, Dr. Rohr was Assistant and Associate Professor at the Department of Chemistry of the University of Göttingen, Germany and Associate Professor at the Department of Pharmaceutical Sciences of the Medical University of South Carolina, Charleston, SC.

Selected Honors

  • Robert A. Blouin Excellence in Pharmaceutical Graduate Education Award for Academic Year (2006)
  • Honor Member, Rho Chi Pharmaceutical Society (2005)
  • Fellow of the Royal Society of Chemistry (FRSC) (2004)
  • Research and Scholarly Activity Award, Medical University of South Carolina, College of Pharmacy (2001)

Selected Publications/Presentations

  • K. A. Shaaban, M. D. Shepherd, T. A. Ahmed, S. E. Nybo, M. Leggas, J. Rohr*: Pyramidamycins A-D and 3-Hydroxyquinoline-2-carboxamide; Cytotoxic Benzamides from Streptomyces sp. DGC1, J. Antibiot. 2012, 65, accepted.
  • G. Wang, P. Pahari, M. K. Kharel, S. G. Van Lanen, J. Rohr*: In Vitro Studies Reveal Two Bifunctional Enzymes Involved in the Biosynthesis of Deoxysugars of the Antitumor Antibiotic Mithramycin, Angew. Chem. 2012, accepted.
  • M. Bosserman, T. Downey, N. Noinaj, , S. K. Buchanan, J. Rohr *: Premithramycin B-Bound Crystal Structure Provides Molecular Insight into Substrate Recognition and Catalysis in the Baeyer−Villiger Monooxygenase MtmOIV, J. Biol. Chem. 2012, under revision.
  • N. Tibrewal, T. E. Downey, S. G. Van Lanen, E. Ul Sharif, G. A. O'Doherty, J. Rohr*: Roles of the Synergistic Reductive O-Methyltransferase GilM and of O-Methyltransferase GilMT in the Gilvocarcin Biosynthetic Pathway, J. Am. Chem. Soc. 2012, 134, 12402-12405. PMID:22800463.
  • K. A. Shaaban, T. A. Ahmed, M. Leggas, J. Rohr*: Saquayamycins G-K, Cytotoxic Angucyclines from Streptomyces sp. Including Two Analogues Bearing the Aminosugar Rednose, J. Nat. Prod. 2012, 75, 1383-1392. PMID:22758660.
  • L. E. Núñez, S. E. Nybo, J. González-Sabín, M. Pérez, N. Menéndez, A. F. Braña, K. A. Shaaban, M. He, F. Morís, J. A. Salas, J. Rohr*, C. Méndez*: A Novel Mithramycin Analogue with High Antitumor Activity and Less Toxicity Generated by Combinatorial Biosynthesis, J. Med. Chem. 2012, 55, 5813-5825. PMID:22578073.
  • M. K. Kharel, J. Rohr*: Delineation of Gilvocarcin, Jadomycin, and Landomycin Pathways through Combinatorial Biosynthetic Enzymology, Curr. Opin. Chem. Biol. 2012, 16, 150-161. PMID:22465094.
  • M. K. Kharel, P. Pahari, K. A. Shaaban, G. Wang, C. Morris, J. Rohr*: Elucidation of Post-PKS Tailoring Steps Involved in Landomycin Biosynthesis, Org. Biomol. Chem. 2012, 10, 4256-4265. PMID:22454092.
  • I. Garcia, N. M. Vior, A. F. Braña, J. G. Sabin, J. Rohr, F. Morís, C. Méndez, J. A. Salas: Elucidating the Biosynthetic Gene Cluster for the Hybrid Polyketide-Nonribosomal Peptide Collismycin A: Unusual Mechanisms for the Formation of the 2,2'-Bipyridyl Ring, Chem. Biol. 2012, 19, 399-413. PMID:22444595.
  • S. E. Nybo, K. A. Shaaban, M. K. Kharel, J. A. Salas, C. Méndez, H. Sutardjo, J. Rohr*: Ketoolivosyl-tetracenomycin C: A New Ketosugar Bearing Tetracenomycin Reveals New Insight into the Substrate Flexibility of Glycosyltransferase ElmGT, Bioorg. Med. Chem. Lett. 2012, 22, 2247-2250. PMID:22361136.
  • P. Patrikainen, P. Kallio, K. D. Klika, K. Fan, P. Mäntsälä, K. A. Shaaban, J. Rohr, K. Yang, J. Niemi, M. Metsä-Ketelä*: Engineering Angucycline Biosynthetic Pathways Through Combinatorial Enzymatic Synthesis, Chem. Biol. 2012, 19, 647-655. PMID:22633416.
  • P. Pahari, M. K. Kharel, M. D. Shepherd, S. G. Van Lanen, J. Rohr*: Enzymatic Total Synthesis of Defucogilvocarcin M and Its Implications for Gilvocarcin Biosynthesis, Angew. Chem Int. Ed. 2012, 51, 1216-1220. PMID:22223167.
  • M. K. Kharel, P. Pahari, M. D. Shepherd, N. Tibrewal, S. E. Nybo, K. A. Shaaban, J. Rohr*: Angucyclines: Biosynthesis, Mode-of-action, New Natural Products, and Synthesis, Nat. Prod. Rep. 2012, 29, 264-325. PMID:22186970.
  • D. Scott, J. Rohr, Y. Bae*: Nanoparticle Formulations of Mithramycin Analogs for Enhanced Cytotoxicity, Int. J. Nanomed. 2011, 6, 2757-2767. PMID22114504.
  • G. Wang, M. K. Kharel, P. Pahari, J. Rohr*: Investigating Mithramycin Deoxysugar Biosynthesis: Enzymatic Total Synthesis of TDP-D-Olivose, ChemBioChem 2011, 12, 2568-2571. PMID: 21960454.
  • S. F. Sleiman, J. Berlin, M. Basso, S. S. Karuppagounder, J. Rohr, R. R. Ratan*: Histone deacetylase inhibitors and mithramycin A impact a similar neuroprotective pathway at a cross road between cancer and neurodegeneration, Pharmaceuticals 2011, 4, 1183-1195 (doi: 10.3390/ph4081183).
  • N. Noinaj, M. A. Bosserman, M. A. Schickli, G. Piszczek, M. K. Kharel, P. Pahari, S. K. Buchanan, J. Rohr*: The Crystal Structure and Mechanism of an Unusual Oxidoreductase, GilR, Involved in Gilvocarcin V Biosynthesis, J. Biol. Chem. 2011, 286, 23533-23543. PMID 215618534.
  • S. F. Sleiman, B. Langley, M. Basso, X. Li, J. B. Payappilly, M. K. Kharel, H. Guo, J. L. Marsh, L. M. Thompson, L. Mahishi, P. Ahuja, W. R. MacLellan, D. Geschwind, G. Coppola, J. Rohr, R. R. Ratan*: Mithramycin is a gene selective Sp1 inhibitor that identifies a biological intersection between cancer and neurodegeneration, J. Neurosci. 2011, 31, 6858-6870. PMID 21543616.
  • M. K. Kharel, H. Lian, J. Rohr*: Characterization of the TDP-D-Ravidosamine Biosynthetic Pathway: One-Pot Enzymatic Synthesis of TDP-D-Ravidosamine from Thymidine-5'-phosphate and Glucose-1-Phosphate, Org. Biomol. Chem. 2011, 9, 1799-1808 PMID21264378.
  • K. A. Shaaban, S. Srinivasan, R. Kumar, C. Damodaran, J. Rohr*: Landomycins P-W, Cytotoxic Angucyclines from Streptomyces cyanogenus S136. J. Nat. Prod. 2011, 74, 2-11 PMID 21188999.
  • M. D. Shepherd, T. Liu, C. Méndez, J. A. Salas, J. Rohr*: Engineered Biosynthesis of Gilvocarcin Analogues with Altered Deoxypyranose Moieties, Appl. Environ. Microbiol. 2011, 77, 435-441. PMID 21075894.
  • Z. Yang, X. Chi., M. Funabashi, S. Baba, K. Nonaka, P. Pahari, J. Unrine, J. M. Jacobsen, G. I. Elliott, J. Rohr, S. G. Van Lanen*: Characterization of LipL as a non-heme, Fe(II)-dependent alpha-ketoglutarate:UMP dioxygenase that generates uridine-5'-aldehyde during A-90289 biosynthesis. J. Biol. Chem. 2011, 286, 7885-7892. PMID 21216959.
  • M. A. Bosserman, A. Florez, K. A. Shaaban, A. F. Braña, J. A. Salas, C. Méndez, J. Rohr*: Characterization of the Terminal Activation Step Catalyzed by Oxygenase CmmOIV of the Chromomycin Biosynthetic Pathway from Streptomyces griseus, Biochemistry 2011, 50, 1421-1428. PMID 21244022.
  • K. A. Shaaban, C. Stamatkin, C. Damodaran, J. Rohr*: 11-Deoxylandomycinone and landomycins X-Z, new cytotoxic angucyclin(on)es from a Streptomyces cyanogenus K62 mutant strain, J. Antibiot. 2011, 64, 64, 141-150. PMID 20978514.
  • J. Rohr: Modifying Oxidation and Glycosylation Events in Biosyntheses of Natural Product Anticancer Drugs – Challenges for Combinatorial Biosynthesis, in Functional Molecules from Natural Sources, S. Wrigley, R. Thomas, C.T. Bedford, N. Nicholson, ed., RSC Publishing, Royal Society of Chemistry, Cambridge, 2011, pp 161-183.
  • S. Previdi, A. Malek, V. Albertini, C. Riva, C. Capella, M. Broggini, G. M. Carbone, J. Rohr and C. V. Catapano*: Inhibition of Sp1 dependent transcription and antitumor activity of the new aureolic acid analogues Mithramycin SDK and SK in human ovarian cancer xenografts, Gyn. Oncol. 2010, 118, 182-188. PMID: 20452660.
  • M. K. Kharel, M. D. Shepherd, S. E. Nybo, M. A. Bosserman, J. Rohr: Isolation of Streptomyces species from Soil, Curr. Protoc. Microbiol. 2010, Chapter 10: Unit 10E.4. PMID 21053254 .
  • R. Kumar, S. Srinivasan, P. Pahari, J. Rohr, C. Damodaran*: Activating Stress-Activated Protein Kinase-Mediated Cell Death and Inhibiting Epidermal Growth Factor Receptor Signaling: A Promising Therapeutic Strategy for Prostate Cancer, Mol. Cancer Ther. 2010, 9, 2488-2496. PMID:20736346 .
  • S. E. Nybo, M. D. Shepherd, M. A. Bosserman, J. Rohr: Genetic Manipulation of Streptomyces Species, Curr. Protoc. Microbiol. 2010, Chapter 10: Unit 10E.3. PMID 21053253.
  • M. D. Shepherd, M. K. Kharel, L. L. Zhu, S. G. Van Lanen, J. Rohr: Delineating the Earliest Steps of Gilvocarcin Biosynthesis: Role of GilP and GilQ in Starter Unit Specificity, Org. Biomol. Chem. 2010, 8, 3851-3856. PMID 20617244.
  • M. A. Bosserman, M. D. Shepherd, M. K. Kharel, J. Rohr: Laboratory Maintenance of Streptomyces argillaceus and Streptomyces griseus, Curr. Protoc. Microbiol. 2010, Chapter 10: Unit 10E.2 PMID 21053252.
  • M. K. Kharel, P. Pahari, H. Lian, J. Rohr: Enzymatic Total Synthesis of Rabelomycin, an Angucycline Group Antibiotic, Org. Lett. 2010, 8, 3851-3856. PMID 2086694.
  • M. D. Shepherd, M. K. Kharel, M. A. Bosserman, J. Rohr: Laboratory Maintenance of Streptomyces species, Curr. Protoc. Microbiol. 2010, Chapter 10: Unit 10E.1 PMID 20812215.
  • M. K. Kharel, S. E. Nybo, M. D. Shepherd, J. Rohr: Cloning and Characterization of the Ravidomycin and Chrysomycin Biosynthetic Gene Clusters, ChemBioChem 2010, 11, 523-532. PMID: 20140934.
  • J. Rohr*, C. Hertweck: Type II PKS, in Comprehensive Natural Products II-Chemistry and Biology, Volume 1 - Structural Diversity I (Fatty Acids, Polyketide Synthases, Terpenes), ISBN-13: 978-0-08-045381-1, L. Mander, H.-W. Liu, ed., Elsevier, Oxford, 2010, pp 227-303.
  • B. Ostash, I. Ostash, L. Zhu, M. K. Kharel, A. Luzhetskyy, A. Bechthold, S. Walker, J. Rohr, V. Fedorenko*: Properties of lanK-based regulatory circuit involved in landomycin biosynthesis in Streptomyces cyanogenus S136, Russian J. Genet. 2010, 46, 530-535.
  • M. Beam, M. A. Bosserman, N. Noinaj, M. Wehenkel, J. Rohr*: Crystal Structure of Baeyer-Villiger Monooxygenase MtmOIV, the Key Enyzme of the Mithramycin Biosynthetic Pathway, Biochemistry 2009, 48, 4476-4487.
  • M. K. Kharel, P. Pahari, H. Lian, J. Rohr*: GilR, and Unusual Lactone-Forming Enzyme Involved in Gilvocarcin Biosynthesis, ChemBioChem 2009, 10, 1305-1308.
  • S. Koduru, S. Sowmyalakshmi, R. Kumar, J. Rohr, C. Damodaran*: Identification of a Potent Herbal Molecule for the Treatment of Breast Cancer, BMC Cancer 2009, 9:41.
  • P. Pahari, J. Rohr*: Total Synthesis of Psoralidin, an Anticancer Natural Product, J. Org. Chem. 2009, 74, 2750-2754.
  • T. Liu, M. K. Kharel, L. Zhu, S. A. Bright, C. Mattingly, V. R. Adams, J. Rohr*: Inactivation of the Ketoreductase gilU Gene of the Gilvocarcin Biosynthetic Gene Cluster Yields New Analogues with Partly Improved Biological Activity. ChemBioChem 2009, 10, 278-286.
  • F. Lombó, M. S. Abdelfattah, A. F. Braña, J. A. Salas, J. Rohr*, C. Méndez*: Elucidation of Oxygenation Steps during Oviedomycin Biosynthesis and Generation of Derivatives with Increased Antitumor Activity. ChemBioChem. 2009, 10, 296-303.
  • R. Kumar, S. Srinivasan, S. Koduru, P. Pahari, J. Rohr, N. Kyprianou, C. Damodaran*: Psoralidin, an Herbal Molecule Inhibits PI3K Mediated Akt Signaling in Androgen Independent Prostate Cancer (AIPC) Cells. Cancer Prevention Res. 2009, 2, 234-243.
  • J. Cain*, E. P. Black, J. Rohr*: An Audience Response System Strategy to Improve Student Motivation, Attention and Feedback in a Physiological Chemistry / Molecular Biology Course. Am. J. Pharm. Educ. 2009, 73(2); Article 21.
  • W. Zhao, L. Zhu, S. Srinivasan, C. Damodaran, J. Rohr*: Identification of Urushioles as the Major Active Principle of the Siddha Herbal Medicine Semicarpus Lehyam: Anti-tumor Agents for the Treatment of Breast Cancer. Pharm. Biol. 2009, 47(9), 886-893.
  • M. S. Abdelfattah, M. K. Kharel, J. A. Hitron, I. Baig, J. Rohr*: Moromycins A and B: Isolation and Structure Elucidation of New C-Glycosylangucycline Type Antibiotics from Streptomyces sp.KY002. J. Nat. Prod. 2008, 71, 1569-1573.
  • M. Pérez, I. Baig, A. F. Braña, J. A. Salas, J. Rohr*, C. Méndez*: Generation of New Derivatives of the Antitumor Antibiotic Mithramycin by Altering the Glycosylation Pattern through Combinatorial Biosynthesis. ChemBioChem 2008, 9, 2295-2304.
  • A. Ramos, F. Lombó, A. F. Braña, J. Rohr, C. Méndez, J. A. Salas*: Biosynthesis of elloramycin in Streptomyces olivaceus requires glycosylation by enzymes encoded outside the aglycon cluster. Microbiology 2008, 154, 781-788.
  • C. Olano, M. S. Abdelfattah, S. Gullón, A. F. Braña, J. Rohr, C. Méndez, J. A. Salas*: Glycosylated Derivatives of Steffimycin: Insights into the Role of the Sugar Moieties for the Biological Activity. ChemBioChem 2008, 9, 624-633.
  • I. Baig, M. Perez, A. F. Braña, R. Gomathinayagam, C. Damodaran, J. A. Salas, C. Méndez*, J. Rohr*: Mithramycin Analogues Generated by Combinatorial Biosynthesis Show Improved Bioactivity. J. Nat. Prod. 2008, 71, 199-207.
  • M. K. Kharel, L. Zhu, T. Liu, J. Rohr*: Multi-Oxygenase Complexes of the Gilvocarcin and Jadomycin Biosyntheses. J. Am. Chem. Soc. 2007, 129, 3780-3781.
  • L. Zhu, A. Luzhetskyy, M. Luzhetska, C. Mattingly, V. Adams, A. Bechthold*, J. Rohr*: Generation of New Landomycins with Altered Saccharide Pattern through Over-expression of Glycosyltransferase Gene lanGT3 in the Biosynthetic Gene Cluster of Landomycin A in Streptomyces cyanogenus S-136. ChemBioChem 2007, 8, 83-88.
  • I. Baig, M. Kharel, A. Kobylyanskyy, L. Zhu, Y. Rebets, B. Ostash, A. Luzhetskyy, A. Bechthold, V. A. Fedorenko* J. Rohr: On the Acceptor Substrate of C-Glycosyltransferase UrdGT2: Three Prejadomycin C-Glycosides From an Engineered Mutant of Streptomyces globisporus 1912 DlndE(urdGT2). Angew. Chem. Int. Ed., 2006, 45, 7842-7846.
  • M. A. Abdelfattah, J. Rohr: Premithramycinone G, an Early Shunt Product of the Mithramycin Biosynthetic Pathway Accumulated upon Inactivation of Oxygenase MtmOII. Angew. Chem. Int. Ed., 2006, 45, 5685-5689.
  • T. Liu, M. K. Kharel, C. Fischer, A. McCormick, J. Rohr: Inactivation of gilGT Encoding a C-Glycosyltransferase and gilOIII Encoding a P450 Enzyme, Allows the Details of the Late Biosynthetic Pathway to Gilvocarcin V to be Delineated. ChemBioChem 2006, 7, 1070-1077.
  • V. Albertini, A. Jain, S. Vignati, S. Napoli, A. Rinaldi, I. Kwee, M. Nur-e-Alam, J. Bergant, F. Bertoni, G. M. Carbone, J. Rohr, C. V. Catapano*: Novel GC-rich DNA Binding Compounds Produced by a Genetically Engineered Mutant of the Mithramycin Producer S. argillaceus Exhibit Improved Transcriptional Repressor Activity: Implications for Cancer Therapy. Nucleic Acids Res. 2006, 34, 1721-1734.
  • M. Gibson, M. Nur-e-Alam, F. Lipata, M. A. Oliveira, J. Rohr: Characterization of Kinetics and Products of the Baeyer-Villiger Oxygenase MtmOIV, the Key Enzyme of the Biosynthetic Pathway toward the Natural Product Anticancer Drug Mithramycin from Streptomyces argillaceus. J. Am. Chem. Soc. 2005, 127, 17594-17595.
  • U. Rix, C. Wang, Y. Chen, F. M. Lipata, L. L. Remsing Rix, L. M. Greenwell, L. C. Vining, K. Yang*, J. Rohr*: The Oxidative Ring Cleavage in Jadomycin Biosynthesis: A Multistep Oxygenation Cascade in a Biosynthetic Black Box. ChemBioChem 2005, 6, 838-845.
  • M. Nur-e-Alam, C. Méndez, J. A. Salas, J. Rohr*: Elucidation of the Glycosylation Sequence of Mithramycin Biosynthesis: Isolation of 3A-Deolivosylpremithramycin B and Its Conversion to Premithramycin B by Glycosyltransferase MtmGII. ChemBioChem 2005, 6, 632-636.
  • C. Sánchez, L. Zhu, A. F. Braña, A. P. Salas, J. Rohr*, C. Méndez, and J. A. Salas*: Combinatorial Biosynthesis of Antitumor Indolocarbazole Compounds. Proc. Natl. Acad. Sci. USA 2005, 102, 461-466.
  • T. Liu, C. Fischer, C. Beninga, J. Rohr*: Oxidative Rearrangement Processes in the Biosynthesis of Gilvocarcin V. J. Am. Chem. Soc. 2004, 126, 12262-12263.

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