Biocatalysis Using Plant and Metagenomic Enzymes for Organic Synthesis
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Iodine(V) Reagents in Organic Synthesis. Part 4. O-Iodoxybenzoic Acid As a Chemospecific Tool for Single Electron Transfer-Based Oxidation Processes K
Published on Web 02/16/2002 Iodine(V) Reagents in Organic Synthesis. Part 4. o-Iodoxybenzoic Acid as a Chemospecific Tool for Single Electron Transfer-Based Oxidation Processes K. C. Nicolaou,* T. Montagnon, P. S. Baran, and Y.-L. Zhong Contribution from the Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, and Department of Chemistry and Biochemistry, UniVersity of California, San Diego, 9500 Gilman DriVe, La Jolla, California 92093 Received September 4, 2001 Abstract: o-Iodoxybenzoic acid (IBX), a readily available hypervalent iodine(V) reagent, was found to be highly effective in carrying out oxidations adjacent to carbonyl functionalities (to form R,â-unsaturated carbonyl compounds) and at benzylic and related carbon centers (to form conjugated aromatic carbonyl systems). Mechanistic investigations led to the conclusion that these new reactions are initiated by single electron transfer (SET) from the substrate to IBX to form a radical cation which reacts further to give the final products. Fine-tuning of the reaction conditions allowed remarkably selective transformations within multifunctional substrates, elevating the status of this reagent to that of a highly useful and chemoselective oxidant. Introduction In the preceding three papers,1-3 we have presented an array of useful transformations mediated by the iodine(V)-based reagents Dess-Martin periodinane (DMP), o-iodoxybenzoic acid (IBX), and Ac-IBX (see Figure 1). In the current paper, we expand on this theme with a description of a powerful new methodology which employs IBX for the facile and selective oxidation adjacent to carbonyl and aromatic moieties. -
Prof. J. Masson Gulland, F.R.S
702 NATURE November 22, 1947 Vol. 160 The general discussion was opened by Dr. W. K. Slater. He emphasized that the additional production OBITUARIES of food from sources in Great Britain means increased supplies of materials, for example, for additional Prof. J. Masson Gulland, F.R.S. factories and plant for extracting sugar-beet and for IT was with a sense of severe personal loss that housing poultry. The training of the human element his many friends learned of the untimely death of in more efficient methods of cultivation and of Prof. J. M. Gulland, who was a victim of the railway management of stock is likely to be a formidable accident at Goswick on October 26. He was a leading task. He asked whether a true appreciation of the figure in the chemical world, a pioneer worker in immediate future position in Great Britain is rather several important fields of organic chemistry and that the number of calories per person and the biochemistry, and a man of outstanding personal nutritional value of the average diet generally are charm. much more likely to fall than to rise ; and how far John Masson Gulland was born in Edinburgh in this fall could go without acute sequelre. 1898 and was the only son of the late Prof. G. Lovell Dr. N. C. Wright considered that a matter of Gulland, professor of medicine in the University of immediate importance is the prevention of wastage, Edinburgh. Gulland was much devoted to his native from whatever cause, of food already produced. We land, and above all to his native city, which ho must find out, for example, exactly what happens to frequently visited. -
Process for Producing Optically Active Tropinone Monocarboxylic Acid Derivative
Europäisches Patentamt *EP001118674A1* (19) European Patent Office Office européen des brevets (11) EP 1 118 674 A1 (12) EUROPEAN PATENT APPLICATION published in accordance with Art. 158(3) EPC (43) Date of publication: (51) Int Cl.7: C12P 17/10 25.07.2001 Bulletin 2001/30 (86) International application number: (21) Application number: 99929794.8 PCT/JP99/03754 (22) Date of filing: 12.07.1999 (87) International publication number: WO 00/18946 (06.04.2000 Gazette 2000/14) (84) Designated Contracting States: • NAKAMURA, Soichi, Nihon Medi-physics K. K. AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU Sodegaura-shi, Chiba 299-0241 (JP) MC NL PT SE • NAKAMURA, Daisaku Ichihara-shi, Chiba 299-0115 (JP) (30) Priority: 30.09.1998 JP 27786898 (74) Representative: Keen, Celia Mary (71) Applicant: Nihon Medi-Physics Co., Ltd. J.A. Kemp & Co. Nishinomiya-shi, Hyogo 662-0918 (JP) 14 South Square Gray’s Inn (72) Inventors: London WC1R 5JJ (GB) • NODE, Manabu Hirakata-shi, Osaka 573-1118 (JP) (54) PROCESS FOR PRODUCING OPTICALLY ACTIVE TROPINONE MONOCARBOXYLIC ACID DERIVATIVE (57) An optically active tropinonemonocarboxylic tained from natural cocaine, it was proved that the ob- acid ester derivative useful as an intermediate for syn- tained optically active tropinonemonocarboxylic acid es- thesis of optically active tropane derivatives was ob- ter derivative had the same absolute configuration as tained by reacting succindialdehyde with an organic that of natural cocaine. The yield of the optically active amine and acetonedicarboxylic acid ester to obtain a tropinonemonocarboxylic acid ester derivative from the tropinonedicarboxylic acid ester derivative, and then asymmetric dealkoxycarbonylation was 30 to 50 mol%, subjecting this derivative to enzyme-catalyzed asym- and its optical purity was 70 to 97%ee. -
Enzyme DHRS7
Toward the identification of a function of the “orphan” enzyme DHRS7 Inauguraldissertation zur Erlangung der Würde eines Doktors der Philosophie vorgelegt der Philosophisch-Naturwissenschaftlichen Fakultät der Universität Basel von Selene Araya, aus Lugano, Tessin Basel, 2018 Originaldokument gespeichert auf dem Dokumentenserver der Universität Basel edoc.unibas.ch Genehmigt von der Philosophisch-Naturwissenschaftlichen Fakultät auf Antrag von Prof. Dr. Alex Odermatt (Fakultätsverantwortlicher) und Prof. Dr. Michael Arand (Korreferent) Basel, den 26.6.2018 ________________________ Dekan Prof. Dr. Martin Spiess I. List of Abbreviations 3α/βAdiol 3α/β-Androstanediol (5α-Androstane-3α/β,17β-diol) 3α/βHSD 3α/β-hydroxysteroid dehydrogenase 17β-HSD 17β-Hydroxysteroid Dehydrogenase 17αOHProg 17α-Hydroxyprogesterone 20α/βOHProg 20α/β-Hydroxyprogesterone 17α,20α/βdiOHProg 20α/βdihydroxyprogesterone ADT Androgen deprivation therapy ANOVA Analysis of variance AR Androgen Receptor AKR Aldo-Keto Reductase ATCC American Type Culture Collection CAM Cell Adhesion Molecule CYP Cytochrome P450 CBR1 Carbonyl reductase 1 CRPC Castration resistant prostate cancer Ct-value Cycle threshold-value DHRS7 (B/C) Dehydrogenase/Reductase Short Chain Dehydrogenase Family Member 7 (B/C) DHEA Dehydroepiandrosterone DHP Dehydroprogesterone DHT 5α-Dihydrotestosterone DMEM Dulbecco's Modified Eagle's Medium DMSO Dimethyl Sulfoxide DTT Dithiothreitol E1 Estrone E2 Estradiol ECM Extracellular Membrane EDTA Ethylenediaminetetraacetic acid EMT Epithelial-mesenchymal transition ER Endoplasmic Reticulum ERα/β Estrogen Receptor α/β FBS Fetal Bovine Serum 3 FDR False discovery rate FGF Fibroblast growth factor HEPES 4-(2-Hydroxyethyl)-1-Piperazineethanesulfonic Acid HMDB Human Metabolome Database HPLC High Performance Liquid Chromatography HSD Hydroxysteroid Dehydrogenase IC50 Half-Maximal Inhibitory Concentration LNCaP Lymph node carcinoma of the prostate mRNA Messenger Ribonucleic Acid n.d. -
Tropinone Synthesis Via an Atypical Polyketide Synthase and P450-Mediated Cyclization
ARTICLE DOI: 10.1038/s41467-018-07671-3 OPEN Tropinone synthesis via an atypical polyketide synthase and P450-mediated cyclization Matthew A. Bedewitz 1, A. Daniel Jones 2,3, John C. D’Auria 4 & Cornelius S. Barry 1 Tropinone is the first intermediate in the biosynthesis of the pharmacologically important tropane alkaloids that possesses the 8-azabicyclo[3.2.1]octane core bicyclic structure that defines this alkaloid class. Chemical synthesis of tropinone was achieved in 1901 but the 1234567890():,; mechanism of tropinone biosynthesis has remained elusive. In this study, we identify a root- expressed type III polyketide synthase from Atropa belladonna (AbPYKS) that catalyzes the formation of 4-(1-methyl-2-pyrrolidinyl)-3-oxobutanoic acid. This catalysis proceeds through a non-canonical mechanism that directly utilizes an unconjugated N-methyl-Δ1-pyrrolinium cation as the starter substrate for two rounds of malonyl-Coenzyme A mediated decarbox- ylative condensation. Subsequent formation of tropinone from 4-(1-methyl-2-pyrrolidinyl)-3- oxobutanoic acid is achieved through cytochrome P450-mediated catalysis by AbCYP82M3. Silencing of AbPYKS and AbCYP82M3 reduces tropane levels in A. belladonna. This study reveals the mechanism of tropinone biosynthesis, explains the in planta co-occurrence of pyrrolidines and tropanes, and demonstrates the feasibility of tropane engineering in a non- tropane producing plant. 1 Department of Horticulture, Michigan State University, East Lansing, MI 48824, USA. 2 Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA. 3 Department of Chemistry, Michigan State University, East Lansing, MI 48824, USA. 4 Department of Chemistry & Biochemistry, Texas Tech University, Lubbock, TX 79409, USA. -
December Cume
Organic Cumulative Exam December 1, 2001 The Chemistry of Professor Eric Sorenson (PLEASE WRITE ALL ANSWERS ON THE FRONT PAGE OF THE EXAM) Professor Sorenson often derives ideas for his synthetic approaches by speculating on the reactions that are involved in the biosynthesis of the target molecule. That is, his synthetic approaches are "biomimetic". Sorenson also noted that this is not a new approach in organic synthesis. He cited Sir Robert Robinson's synthesis of tropinone. Long, long ago, Robinson took heed of the suggestion that enzymatic Mannich reactions might be involved in the biosynthesis of some alkaloids and used a Mannich reaction to prepare tropinone. (J. Chem. Soc. 1917, 762) 1. Give the structure of tropinone and show a detailed mechanism for the reaction: Hint: Remember that intramolecular reactions are faster than analogous intermolecular reactions. O O H+ H + CH3NH2 + H O Tropinone Hint: formula C8H13NO 2. Some questions regarding Professor Sorenson's synthesis of (-)-hispidospermidin (shown below): J. Am. Chem. Soc. 2000, 122, 9556. Reagents and conditions: (a) 2,4,6-triisopropylbenzenesulfonyl hydrazide, HCl (1.2 equiv), CH3CN, room temperature, 75%. (b) n-BuLi (2.05 equiv), Et2O/THF, -78 to -20 C; then MgBr2·OEt2, -78 C; then 7, -78 C to room temperature, 55% from 8. (c) SEMCl, n-Bu4NI, i-Pr2NEt, CH2Cl2, 50 C, ca. 100%. (d) Dibal-H, toluene, -78 C, 93%. (e) (COCl)2, DMSO, CH2Cl2, -78 C; then i-Pr2NEt, -78 C to room temperature, ca. 100%. (f) AcOH, room temperature, 2 d, 83% or AcOH, 80 C, 3 h, 87%. (g) (COCl)2, DMSO, CH2Cl2, -78 C; then i-Pr2NEt, -78 C to room temperature, ca. -
Tropane and Granatane Alkaloid Biosynthesis: a Systematic Analysis
Office of Biotechnology Publications Office of Biotechnology 11-11-2016 Tropane and Granatane Alkaloid Biosynthesis: A Systematic Analysis Neill Kim Texas Tech University Olga Estrada Texas Tech University Benjamin Chavez Texas Tech University Charles Stewart Jr. Iowa State University, [email protected] John C. D’Auria Texas Tech University Follow this and additional works at: https://lib.dr.iastate.edu/biotech_pubs Part of the Biochemical and Biomolecular Engineering Commons, and the Biotechnology Commons Recommended Citation Kim, Neill; Estrada, Olga; Chavez, Benjamin; Stewart, Charles Jr.; and D’Auria, John C., "Tropane and Granatane Alkaloid Biosynthesis: A Systematic Analysis" (2016). Office of Biotechnology Publications. 11. https://lib.dr.iastate.edu/biotech_pubs/11 This Article is brought to you for free and open access by the Office of Biotechnology at Iowa State University Digital Repository. It has been accepted for inclusion in Office of Biotechnology Publicationsy b an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. Tropane and Granatane Alkaloid Biosynthesis: A Systematic Analysis Abstract The tropane and granatane alkaloids belong to the larger pyrroline and piperidine classes of plant alkaloids, respectively. Their core structures share common moieties and their scattered distribution among angiosperms suggest that their biosynthesis may share common ancestry in some orders, while they may be independently derived in others. Tropane and granatane alkaloid diversity arises from the myriad modifications occurring ot their core ring structures. Throughout much of human history, humans have cultivated tropane- and granatane-producing plants for their medicinal properties. This manuscript will discuss the diversity of their biological and ecological roles as well as what is known about the structural genes and enzymes responsible for their biosynthesis. -
Effects of a Bacterial ACC Deaminase on Plant Growth
Effects of a bacterial ACC deaminase on plant growth-promotion by Jennifer Claire Czarny A thesis presented to the University of Waterloo in fulfilment of the thesis requirement for the degree of Doctor of Philosophy in Biology Waterloo Ontario, Canada, 2008 c Jennifer Claire Czarny 2008 Author's declaration I hereby declare that I am the sole author of this thesis. This is a true copy of the thesis, including any required final revisions, as accepted by my examiners. I understand that my thesis may be made electronically available to the public. ii Abstract Plants often live in association with growth-promoting bacteria, which provide them with several benefits. One such benefit is the lowering of plant ethylene levels through the action of the bacterial enzyme 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase that cleaves the immediate biosynthetic precursor of ethylene, ACC. The plant hormone ethylene is responsible for many aspects of plant growth and development but under stressful conditions ethylene exacerbates stress symptoms. The ACC deaminase-containing bacterium Pseudomonas putida UW4, isolated from the rhizosphere of reeds, is a potent plant growth- promoting strain and as such was used, along with an ACC deaminase minus mutant of this strain, to study the role of ACC deaminase in plant growth-promotion. Also, transgenic plants expressing a bacterial ACC deaminase gene were used to study the role of this enzyme in plant growth and stress tolerance in the presence and absence of nickel. Transcriptional changes occurring within plant tissues were investigated with the use of an Arabidopsis oligonucleotide microarray. The results showed that transcription of genes involved in hormone regulation, secondary metabolism and the stress response changed in all treatments. -
Metabolic Enzyme/Protease
Inhibitors, Agonists, Screening Libraries www.MedChemExpress.com Metabolic Enzyme/Protease Metabolic pathways are enzyme-mediated biochemical reactions that lead to biosynthesis (anabolism) or breakdown (catabolism) of natural product small molecules within a cell or tissue. In each pathway, enzymes catalyze the conversion of substrates into structurally similar products. Metabolic processes typically transform small molecules, but also include macromolecular processes such as DNA repair and replication, and protein synthesis and degradation. Metabolism maintains the living state of the cells and the organism. Proteases are used throughout an organism for various metabolic processes. Proteases control a great variety of physiological processes that are critical for life, including the immune response, cell cycle, cell death, wound healing, food digestion, and protein and organelle recycling. On the basis of the type of the key amino acid in the active site of the protease and the mechanism of peptide bond cleavage, proteases can be classified into six groups: cysteine, serine, threonine, glutamic acid, aspartate proteases, as well as matrix metalloproteases. Proteases can not only activate proteins such as cytokines, or inactivate them such as numerous repair proteins during apoptosis, but also expose cryptic sites, such as occurs with β-secretase during amyloid precursor protein processing, shed various transmembrane proteins such as occurs with metalloproteases and cysteine proteases, or convert receptor agonists into antagonists and vice versa such as chemokine conversions carried out by metalloproteases, dipeptidyl peptidase IV and some cathepsins. In addition to the catalytic domains, a great number of proteases contain numerous additional domains or modules that substantially increase the complexity of their functions. -
Sandra Cotes.Pmd
ORIENTAL JOURNAL OF CHEMISTRY ISSN: 0970-020 X CODEN: OJCHEG An International Open Free Access, Peer Reviewed Research Journal 2015, Vol. 31, No. (4): Pg. 1937-1941 www.orientjchem.org Chemical Thermodynamics Applied to the Synthesis of Tropinone SANDRA COTES1* and JOSE COTUA2 1Universidad del Norte, Km 5 Antigua Vía a Puerto Colombia, Barranquilla, Colombia. 2Universidad del Atlántico, Km 7 Antigua Vía a Puerto Colombia, Barranquilla, Colombia. *Corresponding autor E-mail: [email protected] http://dx.doi.org/10.13005/ojc/310410 (Received: August 12, 2015; Accepted: October 04, 2015) ABSTRACT The potential energy surface in Robinson’s tropinone synthesis was calculated using molecular modeling tools. The reaction mechanism was studied, and the stability of the accepted reactive species was evaluated. The findings indicated the amino alcohol intermediate had greater stability than the other proposed intermediates. It was also found that in the presence of dicarboxylic acetone, the activation energy decreased by 69.30 kcal/mol compared to that of the reaction in the presence of acetone. Key words: Robinson´s tropinone synthesis, reaction mechanism, potential energy surface. INTRODUCTION react to form an imine intermediate, which in turn reacts with the substrate containing an acidic There is an increasing interest in the hydrogen in the second step. This stepwise synthesis and biosynthesis of alkaloids derived procedure shows benefits in terms of better yields from tropane because of the biological importance and improved reaction rates compared with the of many of these compounds. Many synthetic conventional Mannich reactions4 and also allows studies have focused on cocaine analogues for a better analysis of the reaction mechanism (see derived from tropinone1. -
Title Structural Basis for the Reaction of Tropinone Reductase-II Analyzed
Structural Basis for the Reaction of Tropinone Reductase-II Title Analyzed by X-ray Crystallography( Dissertation_全文 ) Author(s) Yamashita, Atsuko Citation 京都大学 Issue Date 1998-05-25 URL https://doi.org/10.11501/3138614 Right Type Thesis or Dissertation Textversion author Kyoto University Structural Basis for the Reaction of Tropinone Reductase-II Analyzed by X-ray Crystallography Atsuko Yamashita 1998 Contents Contents Contents Abbreviations iv CHAPTER 1 General Introduction 1 CHAPTER 2 Crystallization and Preliminary Crystallographic Study of Tropinone Reductase-11 5 2-1. Introduction 5 2-2. Experimental Procedures 6 Materials 6 Overproduction 7 Purification 7 Measurement of TR-II Activity 8 Crystallization 8 X -ray Diffraction Experiments 8 2-3. Results and Discussion 9 Purification of TR-II 9 Crystallization of TR-II 10 X-ray Diffraction Data Collection using Flash-Cooling Method 12 Crystallographic Data of TR-II Crystals 14 CHAPTER 3 Crystal Structure of Tropinone Reductase-11 17 3-1. Introduction 17 3-2. Experimental Procedures 19 Materials 19 - 1 - Contents Contents N-Terminal Amino Acid Sequence Analysis 19 CHAPTER 5 Preparation of Heavy Atom Derivative Crystals 19 General Conclusion 69 X-ray Diffraction Data Collection 21 Phase Determination 21 Acknow ledgernen ts 71 Phase Improvement and Model Building 21 Structure Refinement 23 References 73 3-3. Results 23 Structure Determination and Refinement 23 List of Publications 77 Subunit Structure 33 Dimer Structure 36 3-4. Discussion 37 Comparison of Crystal Structures between TR-II and TR-I 37 Implication for Stereospecificity of TRs 41 CHAPTER 4 Crystal Structure of Tropinone Reductase-11 Cornplexed with NADP+ and Pseudotropine 4 7 4-1. -
Supplementary. Table S1 a Total of Degs Detected in This Study (Gm) No
Supplementary. Table S1 A total of DEGs detected in this study (Gm) No. genename significance in annotation 1 At1g01020 D2 ARV1__expressed protein, similar to hypothetical protein DDB0188786 [Dictyostelium discoideum] (GB:EAL62332.1); contains InterPro domain Arv1-like protein (InterPro:IPR007290) 2 At1g01100 D2 60S acidic ribosomal protein P1 (RPP1A), similar to 60S ACIDIC RIBOSOMAL PROTEIN P1 GB:O23095 from (Arabidopsis thaliana) 3 At1g01120 D2, Dm KCS1__fatty acid elongase 3-ketoacyl-CoA synthase 1 (KCS1), nearly identical to GB:AAC99312 GI:4091810 from (Arabidopsis thaliana) 4 At1g01160 D1, D2, Dm GIF2__SSXT protein-related / transcription co-activator-related, similar to SYT/SSX4 fusion protein (GI:11127695) (Homo sapiens); supporting cDNA gi:21539891:gb:AY102640.1:; contains Pfam profile PF05030: SSXT protein (N-terminal region) 5 At1g01170 D2 ozone-responsive stress-related protein, putative, similar to stress-related ozone-induced protein AtOZI1 (GI:790583) (Arabidopsis thaliana); contains 1 predicted transmembrane domain; 6 At1g01240 D1, D2, Dm expressed protein 7 At1g01300 D2, Dm aspartyl protease family protein, contains Pfam domain, PF00026: eukaryotic aspartyl protease 8 At1g01320 D2 tetratricopeptide repeat (TPR)-containing protein, low similarity to SP:P46825 Kinesin light chain (KLC) {Loligo pealeii}; contains Pfam profile PF00515: TPR Domain 9 At1g01430 D2, Dm expressed protein, similar to hypothetical protein GB:CAB80917 GI:7267605 from (Arabidopsis thaliana) 10 At1g01470 D1, D2, Dm LEA14_LSR3__late embryogenesis abundant