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Synthases Joe Chappell University of Kentucky, [email protected]

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University of Kentucky UKnowledge Pharmaceutical Sciences Faculty Patents Pharmaceutical Sciences 5-27-2003 Synthases Joe Chappell University of Kentucky, [email protected] Kathleen R. Manna Joseph P. Noel Courtney M. Starks Right click to open a feedback form in a new tab to let us know how this document benefits oy u. Follow this and additional works at: https://uknowledge.uky.edu/ps_patents Part of the Pharmacy and Pharmaceutical Sciences Commons Recommended Citation Chappell, Joe; Manna, Kathleen R.; Noel, Joseph P.; and Starks, Courtney M., "Synthases" (2003). Pharmaceutical Sciences Faculty Patents. 65. https://uknowledge.uky.edu/ps_patents/65 This Patent is brought to you for free and open access by the Pharmaceutical Sciences at UKnowledge. It has been accepted for inclusion in Pharmaceutical Sciences Faculty Patents by an authorized administrator of UKnowledge. For more information, please contact [email protected]. US006569656B2 (12) United States Patent (10) Patent N0.: US 6,569,656 B2 Chappell et al. (45) Date of Patent: *May 27, 2003 (54) SYNTHASES 5,824,774 A 10/1998 Chappell et al. 5,849,526 A 12/1998 Pichersky (75) Inventors: Joseph Chappell, Lexington, KY (US); 5,871,988 A 2/1999 Croteau et al. Kathleen R. Manna, Georgetown, IN 5,876,964 A 3/1999 Croteau et al. (US); Joseph P. Noel, San Diego, CA (List continued on next page.) (US); Courtney M. Starks, La Jolla, CA (US) FOREIGN PATENT DOCUMENTS (73) Assignees: The University of Kentucky Research EP 0 768 381 4/1997 Foundation, Lexington, KY (US); The W0 WO 95/11913 5/1995 Salk Institute for Biological Studies, W0 WO 96/36697 11/1996 W0 WO 97/15584 5/1997 La Jolla, CA (US) W0 WO 97/38571 10/1997 (*) Notice: Subject to any disclaimer, the term of this (List continued on next page.) patent is extended or adjusted under 35 U.S.C. 154(b) by 0 days. OTHER PUBLICATIONS Appl. No.: 09/903,012 Back et al. PNAS USA 1996 vol. 93 pp. 6841—6845.* (21) Lesburg et al., Current Opinion in Structural Biology, 1998, (22) Filed: Jul. 11, 2001 8:695—703. Prior Publication Data Starks et al., “Structural Basis for Cyclic Terpene Biosyn (65) thesis by Tobacco 5—Epi—Aristolochene Synthase,” Science, US 2002/0094557 A1 Jul. 18, 2002 1997, 227:1815—1820. Chappell, “The Biochemistry and Molecular Biology of Related US. Application Data Isoprenoid Metabolism,” Plant Physiol, 1995, 107:1—6. (63) Continuation of application No. 09/398,395, ?led on Sep. (List continued on next page.) 17, 1999, now Pat. No. 6,468,772. (60) Provisional application No. 60/150,262, ?led on Aug. 23, 1999, provisional application No. 60/130,628, ?led on Apr. Primary Examiner—Marianne P. Allen 22, 1999, and provisional application No. 60/100,993, ?led Assistant Examiner—Lori A. CloW on Sep. 18, 1998. (74) Attorney, Agent, or Firm—Fish & Richardson P.C., PA. (51) Int. Cl.7 .......................... .. C12N 9/00; C12N 9/88; C07H 21/04 (57) ABSTRACT (52) US. Cl. ......................... .. 435/183; 435/4; 435/232; 435/468; 536/232; 536/111; 585/355; Novel synthases and the corresponding nucleic acids encod 524/9 ing such synthases are disclosed herein. Such synthases (58) Field of Search ............................... .. 435/183, 193, possess an active site pocket that includes key amino acid 435/4, 232, 468; 536/111, 23.2; 585/355; residues that are modi?ed to generate desired terpenoid 524/9; 558/12 reaction intermediates and products. Synthase modi?cations are designed based on, e.g., the three-dimensional coordi (56) References Cited nates of tobacco 5-epi-aristolochene synthase, With or With out a substrate bound in the active site. U.S. PATENT DOCUMENTS 5,589,619 A 12/1996 Chappell et al. 11 Claims, 4 Drawing Sheets CC'OH terminus (54a) N12 terminus {17'} US 6,569,656 B2 Page 2 US. PATENT DOCUMENTS Chen et al., “Cloning, Expression, and Characterization of (+)—6—Cadinene Synthase: A Catalyst for Cotton Phytoal 5,891,697 A 4/1999 Croteau et 211. exin Biosynthesis,” Arch. Biochem. Biophys., 1995, 5,981,843 A 11/1999 Chappell et 211. 5,994,114 A 11/1999 Croteau et 211. 324(2):255—266. 6,008,043 A 12/1999 Croteau et a1. Bohlmann et al., “Plant terpenoid synthases: Molecular biology and phylogenetic analysis,” Proc. Natl. Acad. Sci. FOREIGN PATENT DOCUMENTS USA, 1998, 95:4126—4133. Cane et al., “Trichodiene Synthase. Substrate Speci?city and W0 WO 97/38703 10/1997 Inhibition,” Biochemistry, 1995, 34:2471—2479. W0 WO 99/02030 1/1999 W0 WO 99/15624 4/1999 Pyun et al., “Regiospeci?ciy and Isotope Effects Associated W0 WO 99/18118 4/1999 With the Methyl—Methylene Eliminations in the Enzyme— W0 WO 99/19460 4/1999 Catalyzed Biosynthesis of (R)— and (S)—Limonene,” J. Org. W0 WO 99/37139 7/1999 Chem, 1993, 58(15)3998—4009. W0 WO 99/38957 8/1999 Anderson et al., “Farnesyl Diphosphate Synthetase—Mo lecular Cloning, Sequence, and Expression of an Essential OTHER PUBLICATIONS Gene From Saccharomyces cerevisiae, ” J. Biol. Chem, 1989, 264(32):19176—19184. Facchini et al, “Gene family for an elicitor—induced sesquit Song et al., “Yeast farnesyl—diphosphate synthase: Site—di erpene cyclase in tobacco,” Proc. Natl. Acad. Sci. USA, rected mutagenesis of residues in highly conserved prenyl 1992, 89:11088—11092. transferase domains I and II,” Proc. Natl. Acad. Sci. USA, Corey et al., “Isolation of an Arabidopsis thaliana gene 1994, 91:3044—3048. encoding cycloartenol synthase by functional expression in Ohnuma et al., “A Role of the Amino Acid Residue Located a yeast mutant lacking lanosterol synthase by the use of a on the Fifth Position before the First Aspartate—rich Motif of chromatographic screen,” Proc. Natl. Acad. Sci. USA, 1993, Farnesyl Diphosphate Synthase on Determination of the 90:11628—11632. Final Product,”J. Biol. Chem, 1996, 271(48):30748—30754. Bohlmann et al., “Terpenoid—based defenses in conifers: Tarshis et al., “Regulation of product chain length by iso cDNA cloning, characterization, and functional expression prenyl disphosphate synthases,” Proc. Natl. Acad. Sci. USA, of Wound—inducible (E)—ot—bisabolene synthase from grand 1996, 93:15018—15023. ?r (Abies grandis),” Proc. Natl. Acad. Sci. USA, 1998, Tarshis et al., “Crystal Structure of Recombinant Farnesyl 95:6756—6761. Diphosphate Synthase at 2.6—A Resolution,” Biochemistry, Colby et al., “Germacrene C synthase from Lycopersicon 1994, 33:10871—10877. esculentum cv. VFNT Cherry tomato: cDNA isolation, char Mau et al., “Cloning of casbene synthase cDNA: Evidence acterization, and bacterial expression of the multiple product for conserved structural features among terpenoid cyclases sesquiterpene cyclase,” Proc. Natl. Acad. Sci. USA, 1998, in plants,” Proc. Natl. Acad. Sci. USA, 1994, 91:8497—8501. 95:2216—2221. Wendt et al., “Structure and Function of a Squalene Devarenne et al., “Molecular Characterization of Tobacco Cyclase,” Science, 1997, 277:1811—1815. Squalene Synthase and Regulation in Response to Fungal Cane et al., “Trichodiene Synthase. Identi?cation of Active Elicitor,” Arch. Biochem. Biophys., 1998, 349(2):205—215. Site Residues by Site—Directed Mutagenesis,” Biochemistry, 1995, 34:2480—2488. Back et al., “Cloning and Bacterial Expression of a Sesquit Cane et al., “Trichodiene Biosynthesis and the Stereochem erpene Cyclase from Hyoscyamus muticus and Its Molecular istry of the Enzymatic Cyclization of Farnesyl Pyrophos Comparison to Related Terpene Cyclases,” J. Biol. Chem, phate,” Bioorg. Chem, 1985, 13(3):246—265. 1995, 270(13):7375—7381. Wheeler et al., “Direct demonstration of the isomerization Yin et al., “Regulation of Sesquiterpene Cyclase Gene component of the monoterpene cyclase reaction using a Expression—Characterization of an Elicitor— and Pathogen— cyclopropylcarbinyl pyrophosphate substrate analog,” Proc. Inducible Promoter,” Plant Physiol., 1997, 115:437—451. Natl. Acad. Sci. USA, 1987, 84(14):4856—4859. Mathis et al., “Pre—Steady—State Study of Recombinant Pyun et al., “Sterochemistry of the Proton Elimination in the Sesquiterpene Cyclases,” Biochemistry, 36(27):8340—8348. Formation of (+)— and (—)—ot—Pinene by Monterpene Cycla Back et al., “Identifying functional domains With terpene ses from Sage (Salvia O?icinalis),” Arch. Biochem. Bio cyclases using a domain—sWapping strategy,” Proc. Natl. phys.,1994, 308(2):488—496. Acad. Sci. USA, 1996, 93:6841—6845. Croteau, “Evidence for the Ionization Steps in Monoterpene Cyclization Reactions Using 2—Fluorogeranyl and 2—Fluo NeWman et al., “Characterization of the TAC box, a cis—ele rolinalyl Pyrophosphates as Substrates,” Arch. Biochem. ment Within an elicitor—inducible sesquiterpene cyclase pro Biophys., 1986, 251(2):777—782. moter,” Plant J., 1998, 16(1):1—12. Croteau et al., “Irreversible Inactivation of Monoterpene Crock et al., “Isolation and bacterial expression of a ses Cyclases by a Mechanism—Based Inhibitor,”Arch. Biochem. quiterpene synthase cDNA clone from peppermint (Mentha Biophys., 1993, 307(2):397—404. ><piperita, L.) that produces the aphid alarm pheromone Rajaonarivony et al., “Characterization and Mechanism of (E)—[3—farnesene,” Proc. Natl. Acad. Sci. USA, 1997, (4S)—Limonene Synthase, A Monoterpene Cyclase from the 94:12833—12838. Glandular Trichomes of Peppermint (Mentha ><piperita),” Wildung et al., “A cDNA Clone for Taxadiene Synthase, the Arch. Biochem. Biophys., 1992, 296(1):49—57. Diterpene Cyclase That Catalyzes the Committed Step of Rajaonarivony et al., “Evidence for an Essential Histidine Taxol Biosynthesis,” J. Biol. Chem, 1996, Residue in 4S—Limonene Synthase and Other Terpene 271(16):9201—9204. Cyclases,” Arch. Biochem. Biophys. 1992, 299(1):77—82. US 6,569,656 B2 Page 3 Aleshin et a1., “Re?ned Crystal Structures of Glucoarnylase Starks et a1., “Structural Basis for Cyclic Terpene Biosyn from Aspergillus awamori var. X100,” J. Mol. Biol., 1994, thesis by Tobacco 5—Epi—Aristolochene Synthase”, Science, 238:575—591. 1997, 277:1815—1819.
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    USOO6610527B1 (12) United States Patent (10) Patent No.: US 6,610,527 B1 Croteau et al. (45) Date of Patent: Aug. 26, 2003 (54) COMPOSITIONS AND METHODS FOR Facchini et al., “Gene family for an Elicitor-Induced Ses TAXOL BIOSYNTHESIS quiterpene Cyclase in Tobacco,” Proc. Natl. Acad. Sci. USA 89:11088–11092 (1992). (75) Inventors: Rodney B. Croteau, Pullman, WA FloSS et al., in Taxol: Science and Applications, Suffness (US); Mark R. Wildung, Colfax, WA (ed.), pp. 191-208, CRC Press, Boca Raton, FL (1995). (US) Hezari et al., “Purification and Characterization of Taxa-4(5), 11(12)-diene Synthase from Pacific Yew (Taxus (73) Assignee: Washington State University Research brevifolia) that Catalyzes the First Committed Step of Taxol Foundation, Pullman, WA (US) Bosynthesis,” Arch. Biochem. BiophyS. 322:437-444 (1995). * Y NotOtice: Subjubject to anyy disclaimer,disclai theh term off thisthi Hezari et al., “Taxol Biosynthesis: An Update,” Planta Med. patent is extended or adjusted under 35 63:291-295 (1997). U.S.C. 154(b) by 162 days. Hezari et al., “Taxol Production and Taxadiene Synthase Activity in Taxus canadensis Cell Suspension Cultures,” (21) Appl. No.: 09/593,253 Arch. Biochem. Biophy. 337:185-190 (1997). Koepp et al., “Cyclization of Geranylgeranyl Diphosphate to (22) Filed: Jun. 13, 2000 Taxa-4(5), 11(12)-diene Is the Committed Step of Taxol Related U.S. Application Data Biosynthesis in Pacific Yew,” J. Biol. Chem. 270:8686-8690 (1995). (60) Continuation of application No. 09/315.861, filed on May LaFever et al., “Diterpenoid Resin Acid Biosynthesis in 20, 1999, now Pat.
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    New Biotechnology · Volume 31S · July 2014 SUNDAY 13 JULY INDUSTRIAL BIOTECHNOLOGY FROM FUNDAMENTALS TO PRACTICE (ACIB SESSION) Orals Sunday 13 July References Industrial biotechnology from fundamentals [1].Tsuji Y, Fujihara T. Chem Commun 2012;48:2365. [2].Glueck SM, Gümüs S, Fabian WMF, Faber K. Chem Soc Rev to practice (ACIB Session) 2010;39:313. [3].Matsui T, Yoshida T, Yoshimura T, Nagasawa T. Appl Microbiol Bio- ACIB-1 technol 2006;73:95. [4].Lindsey AS, Jeskey H. Chem Rev 1957;57:583. Two promising biocatalytic tools: regioselective car- [5].Wuensch C, Gross J, Steinkellner G, Lyskowski A, Gruber K, Glueck boxylation of aromatics and asymmetric hydration of SM, Faber K. RSC Adv 2014;4:9673. alkenes [6].Wuensch C, Gross J, Steinkellner G, Gruber K, Glueck SM, Faber K. Angew Chem Int Ed 2013;52:2293. Silvia M. Glueck 1,∗ , Christiane Wuensch 1, Tamara Reiter 1, http://dx.doi.org/10.1016/j.nbt.2014.05.1615 Johannes Gross 1, Georg Steinkellner 1, Andrzej Lyskowski 1, Karl Gruber 2, Kurt Faber 2 1 ACIB GmbH c/o University of Graz, Department of Chemistry, Austria ACIB-2 2 University of Graz, Austria Unconventional substrates for enzymatic reduction: car- Due to the growing demand for alternative carbon sources, boxylates and nitriles the development of CO2-fixation strategies for the production M. Winkler 1,∗ K. Napora-Wijata 1 B. Wilding 1 N. Klempier 2 of valuable chemicals is a current challenge in synthetic organic , , , chemistry [1]. The enzymatic carboxylation of aromatic com- 1 ACIB GmbH, Petersgasse 14/III, 8010 Graz, Austria 2 pounds [2,3] catalyzed by various decarboxylases represents a Institute of Organic Chemistry, Graz University of Technology, Stremayrgasse promising ‘green’ alternative to the classic Kolbe-Schmitt reaction 9, 8010 Graz, Austria [4] which requires harsh reaction conditions.
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    bioRxiv preprint doi: https://doi.org/10.1101/2021.04.02.438176; this version posted April 2, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 Transcriptomic analysis of resistant and susceptible responses in a new model root-knot 2 nematode infection system using Solanum torvum and Meloidogyne arenaria 3 4 Kazuki Sato1, Taketo Uehara2, Julia Holbein3, Yuko Sasaki-Sekimoto4, Pamela Gan1, Takahiro 5 Bino5, Katsushi Yamaguchi5, Yasunori Ichihashi6, Noriko Maki1, Shuji Shigenobu5, Hiroyuki 6 Ohta4, Rochus B. Franke7, Shahid Siddique3, 8, Florian M. W. Grundler3, Takamasa Suzuki9, 7 Yasu hiro Kad ota 1, *, Ken Shirasu1, 10, * 8 9 1 RIKEN Center for Sustainable Resource Science (CSRS), Yokohama, Japan 10 2 Central Region Agricultural Research Center, National Agriculture and Food Research 11 Organization (NARO), Tsukuba, Japan 12 3 INRES – Molecular Phytomedicine, Rheinische Friedrich-Wilhelms-University of Bonn, 13 Germany 14 4 School of Life Science and Technology, Tokyo Institute of Technology, Yokohama, Japan 15 5 NIBB Core Research Facilities, National Institute for Basic Biology, Okazaki, Japan 16 6 RIKEN BioResource Research Center (BRC), Tsukuba, Japan 17 7 Institute of Cellular and Molecular Botany, Rheinische Friedrich-Wilhelms-University of Bonn, 18 Germany 19 8 Department of Entomology and Nematology, University of California, Davis,