Abietic Acid 156 Acetaldehyde 87, 116 Acetoacetic Acid 14, 35-37

Total Page:16

File Type:pdf, Size:1020Kb

Abietic Acid 156 Acetaldehyde 87, 116 Acetoacetic Acid 14, 35-37 Index Abietic acid 156 Adenylate cyclase 193,194, 197 Acetaldehyde 87, 116 Adenylosuccinate lyase 200 Acetate 36-38,40,43,48,60,61, 72, Adhota vasica 141 117,125,138,141,146,150,158, Adrenaline 190, 197 161, 189 Adrenergic system 185, 189-192 Acetoacetic acid 14, 35-37,60,61 Agglutination 202 Acetonedicarboxylic acid 13, 35, 60 Agmatine 21, 22 Acetylcholine (see Choline, acetyl) coumaroyl- 23 Acids 3, 28, 167 Agonists 186 Aconite 156 Agroclavine 128,129,131,172 Aconitine 156, 157 Aizoaceae 108 Aconitum 155, 157 Ajmalicine 121-123 Acridine 1 37, 139 Ajmaline 114, 117, 119, 121-123, 198 Acridone 139, 140 Alanine 20, 38, 49 Actinidia polygama 154 f3-Alanine 49 Actinidine 154, 155 Alcohol dehydrogenase 198 Addiction 194 Alcoholism 87 Adenine 147 Aldehydes 13,21,23,76,115,167, Adenocarpine 47 169 Adenocarpus Aldol condensation 12 foliosus 37, 47 Alfalfa 28 viscosus 47 Allantoic acid 148 Adenosine 193,195 Allantoin 148 monophosphate, cyclic 193, 195, Alpiniginine 86 197 Amanita 23, 25 triphosphate 197 Amaranthin 150 S-Adenosylmethionine 15,40, 106, Amaranthus 150 148 Amaryllidaceae 105 212 Index Amides 23,26,28,40,167,174 Aristolochic acid 100 Amidines 22 Arthrobacter 173 Amine oxidase 14, 60, 78, 189, 191 colchovorum 176 Amines 20, 167, 191 oxtdans 174, 175 Amino acids 12,15,20,45,46,69,73, Arthropods 3 149, 167, 196 Arundo donax 30 a-Aminoadipic acid 50 Ascorbic acid 198 2-Aminobenzoylacetic acid 138, 141 Aspartic acid 43, 48-50, 141 'Y-Aminobutyric acid 69, 194, 195 imino- 49 2-Amino-3-methylenepentanoic acid Aspergillus 146 fumigatus 131 3-Aminomethylindole 30 ochraceus 1 77 5-Aminopentanal 37, 70 versicolor 175 Ammodendron karelinii 72 Asptdosperma 11 3, 125, 126 Ammonia 7, 38 pyricollum 127 Ammonium 161 Aspidospermine 120, 127 Ammothamnus lehmannii 71 Astrocaria phyllantoides 47 a-Amylase 202 Astrocasine 47 Anabasine 17,18,42,43,46,47,70, Atisine 156, 157 169 ATPase 196, 198 Anagyrine 72, 73 Atropa 5,58 Analogy 4 belladonna 58, 62, 64 Anatabine 43,46 Atropine (see Hyoscyamine) Androcymbine 109 Autumnaline 110, 111 Androcymbium methanthiodes 109 Auxins 7,48, 115, 123, 161 Angustifoline 67, 72 Azaquinones 174 Anhalamine 77 Anhalonidine 77 Anhalonium lewinti" 25 Bacteria 3, 8, 49, 50, 141, 174, 200 Animals 3,30,51, 162, 166, 194 halophilic 198 Annona squamosa 79 Banana 25, 26 Annuloline 26, 110, 111 Baptifoline 68 Antagonists 186 Baptista 67, 72 Anthranilic acid 131,137,142,145, Barley 23, 25, 30 156 Batrachotoxinin A 162, 196 Aphids 69 Beans 17,38,115 Apocynaceae 3, 113, 11 7, 123, 125, Beets 23, 149 158 sugar 21 Apomorphine 191 Belladine 106, 107 Aporphines 91, 100, 170 Benzoic acid 63 Apparicine 127 m-hydroxy- 63 Arabinoside 40 Benzophenanthridines 83, 198,200 Arborine 141 Benzoxazoles 148 Areca catechu 68 Benzoxazolinone 148, 149 Arecaidine 168, 169 6-methoxy- 148 -N-oxide 168 Benzylisoquinolines 2, 77,92, 176 Arecoline 168,187,195 bis- 79, 176 Argemone 99 Berberastine 79, 82 Arginine 21, 22, 62, 69, 161 Berberine 2,3,78,81,82,177, Aristolochia sipho 100 197-200 Index 213 Berbine 170 Carbostyrils 169, 171 Beta vulgaris 23 Carcinogens 168, 199 Betacyanidin 149, 150 Carica papaya 39 Betacyanins 149 Carotenoids 198 Betaine 23, 24, 28, 46 Carpaine 39 Betalains 149 Casimiroa edulis 15 1 Betalamic acid 149, 150 Casimiroine 138 Betaxanthins 149 Cassaine 196 Betel nut 168 Cassia speetabilis 39 Betonicine 28 Castor bean 40 Bicuculline 195 Catecholamines 87,194,197 Biosynthesis 12 Catechol-O-methyltransferase 189, Boldine 92 202 Boraginaceae 144 Catha edulis 40 Bound forms 6, 47, 98 Catharanthine 120, 123, 126,202 Brain 115, 169, 192-195 Catharanthus 11 3, 123 Brownine 156 roseus 6,7,121-123 Bryophytes 3 Catheduline 40 Bryozoans 3 Cathenamine 119-122 Bufotalin 162 Cations 187,190,195 Bufotenine 29,167,195 Cats 168, 171 Bulbocapnine 92 Ceanothine B 24 Butterflies 67, 147, 172 Ceanothus 24 Buxus 158, 159, 162 Cell culture 7,25,48,64,101, 115, 121,123 Cellulose 202 Cacti 25, 76 Cephaeline 85, 86 Cadaverine 14, 17, 21, 22, 36, 37, 46, Cephalotaxine A 87 69, 70, 72, 145 Cephalotaxus 86 Caffeic acid 106 Cerebrosides 193 Caffeine 3, 147, 148, 172, 176, 195, Ceveratum 159, 161 196, 199, 200, 202 Chanoclavine-I 128, 129, 131 Calcium 7,194, 196, 197 Chelerythrine 82, 84 Calmodulin 194 Chelidonine 83, 84 Calycanthine 116 Chelidonium malus 5, 64, 81, 83 Calyeanthus floridus 116 Chimonanthine' 114, 116 Camellia sinensis 148 Chimonanthus fragrans 116 Camptotheea aeuminata 127 p-Chlorophenylalanine 131 Camptothecin 127, 199 Chlorophyll 7,195 Canary grass 29 Chloroplasts 70, 197, 198 Candicine 25, 27 Cholesterol 158,159,161,163,202 Cannabis sativa 23 Choline 23,24,46 Capsaicinoids 28 acetyl- 23, 24, 185-189 Caracurine-VII 124-126 phosphoryl- 23, 24 Caranine 106 Cholinergic system 185, 197 N-Carbamylputrescine 22 Cholinesterase 186, 188 Carbinolamine 13 Cieer arietinum 23 p-Carboline 115 Cinchona 123, 124, 169, 198 Carbon dioxide 18, 42, 45, 46, 72,92, sueeiruba 124 93,95,98,167 Cinchona mine 124 214 Index Cinchonidine 169, 171 Crotolaria spectabitis 144 Cinchonine 169, 171 Croton 94 Cinnamic acid 37,47, 106, 109, 110, /lavens 100 138 linearis 94, 100 hydroxy- 28, 106 sparsifolius 94 Citric acid 13, 60, 197 Crotonosine 94, 100 Claviceps 113,127 Cryptolepsis buchanani 40 purpurea 4, 131 Cryptopine 82 Clavicipitic acid 128 Cularines 87 Clavines 127,131 Cultures 5, 7, 18,48, 64, 80, 87, 95, Clinia miniata 198 101, 115, 123, 130, 138, 148, 158, Cocaine 59-61, 63, 168, 188, 191, 160,194,200 196, 198 Cunninghamella blakesleeana 176 Cochlearin 63 Curare 123, 125, 187 Coclaurine 77, 80, 92, 94, 95 Cuscohygrine 35, 36 N-methyl- 80, 92 Cyanide 49 Codeine 95,96,98, 100, 101, 167, fj-Cyanoalanine 49 171,177 3-Cyano-4-methoxypyridine 42 -methyl ether 95 Cycloartenol 162 Codeinone 95, 96, 100, 101 Cyclohexadienone 93,95 14-hydroxy- 176 Cycloheximide 48, 194, 200 Coffea arabica 148 Cyclomicrophyllin A 162 Coffee 148 Cyclopeptine 139 Colchiceine 198, 199, 202 Cyphomandra 60 Colchicine 1, 109, 110, 176, 200, 201 Cytisine 67-69, 72, 73 Colchicum 109 N-methyl- 72, 73 autumnale 110 Cytisus 67 Compositae 138, 144 laburnum 73 Conarrhimine 163 Cytochrome 167, 198 Conessine 177 Cytokinesis 202 Conhydrine 38, 39 Cytokinins 148, 161 'Y-Coniceine 38 Coniine 2, 38 Conium maculatum 38 Darnascenine 137 Conjugation 167 Daphniphyllum teijsmanni 158 Consolida 155 Datura 5, 6, 58, 62 Convolvulaceae 127 ceratocaula 62 Corn 148 ferox 62 Cornaceae 155 innoxia 60, 62, 64 Corydaline 82 metel 60, 63, 64 Corydalis ochotensis 87 meteloides 62 Corynantheidine 172 stramonium 60, 62-64 Corynantheine 117,119,124,125 Decarboxylases 20,25,28,30,37,69, Corynoxeine 125 128, 1)1 Cotinine 169, 170 Degradation 4, 8, 30, 42, 46, 48, 98 -methonium ion 170 1,2-Dehydroanabasine 46 p-Coumaric acid 74· Dehydrolupanine 73 Cournaroylagmatine 23 Dehydrosparteine 73 Crataegus monogyna 20 Delpheline 156, 157 Crinamine 106, 107 Delphinium 1) 5, 1) 8 Crinine 108 ajacis 1 5 6 Index 215 brownii 156 3,5-Dimethoxy-4-hydroxyphenethyl- elatum 156 amine 26,77 Demecolcine 110 Dimethylallyl pyrophosphate 22, 128 Demethoxyalstonidine 16 Dimethylallyltryptophan 128, 131 Demethylation 5,25,42,44,94,98, Dimethylamine 168 100,167-169,171-174,176 3-Dimethylaminomethylindole (see Demethylcotinine 169, 170 Gramine) Dendrobine 155 L- 3-Dimethylamino-3-phenylpropanoic Dendrobium nobile 155 acid 156 21-Deoxyajmaline 123 Dimethylbenzanthracene 199 Deoxyribonucleic acid 199, 200 6,8-Dimethylergoline 127 -polymerase 199, 200 N-Dimethyltryptamine 29 Desacetylisoipecoside 85 Dioscorea hispida 40 Detoxication 8, 73 Dioscorine 40 Diaboline 125, 126 Dipterin 29 Diamine oxidase 14,23,35,37,44, Diterpenoids 155, 196 46,69, 70, 167, 198 Dogs 167, 171, 173 Diamines 14 Dolichothele sphaerica 150 1,4-Diaminobutane (see Putrescine) Dolichotheline 150,151 1,5-Diaminopentane (see Cadaverine) Dopamine 25-27, 76, 78, 81, 82, 85, 1,5-Diaminopimelic a,cid 50 87,88,92, 191, 193, 194 Dibenzazonine 98 Dropsy 196 Dibenzocyclooctane 99 Duboisia 58, 64 Dibenzopyrrocolines 87 myoporoides 4 Dicentra spectabilis 81 2,4-Dichlorophenoxyacetic acid 48, 123 Echinops ritro 138 Dicotyledons 3, 23 Echinorine 138 Dictamnine 140 Echitamine 122 Dictamnus albus 139 Ecology 5, 8, 68, 161 Dideoxynorlaudanosolinecarboxylic Edulinine 139, 140 acid 87 Ellipticine 172, 176, 198, 199 Dienol-benzene rearrangement 94 9-hydroxy- 176, 198 Digitoxin 196 9-methoxy- 176 Dihydroxyacetone phosphate 21,49 Elymoclavine 128, 129, 131, 172 2,6-Dihydroxy-N-methylmyosmine Embryos 7, 23, 25 175 Emetine 85, 86, 198, 200 2,3-DihydroxY-3-methylpentanoic acid Endorphins 192 146 Enkephalins 192-194 3,4-Dihydroxyphenethylamine (see Enzymes 16, 18, 20, 25, 64, 73, 74, Dopamine) 106,121,138, 148, 160, 164, 3,4-Dihydroxyphenylacetaldehyde 87 173-175,182,183,186, 194, 197 3,4-Dihydroxyphenylacetic acid 25, Ephedra gerardiana 27 87 Ephedrine 27,168,191 3,4-Dihydroxyphenylalanine 25-27, Epistephanine 80 76,78,79,88,97,101,149 Equisetum 3 3,4-Dihydroxyphenylpyruvic acid 78 Ergocornine 200 2,6-Dihydroxypseudooxynicotine 175 Ergocristine 4 3,4-Dihydroxypyridine 38 Ergoline 128 3,4-DimethoxY-5-hydroxymethyl- Ergometrine 130 phenylalanine 26, 76 Ergonovine 130 216 Index Ergot 4, 113, 127, 191, 195 Galanthamine 107, 189 Ergotamine 4, 130 Galanthine 106, 107 Erysopine 99 Galega officinalis 22 Erythraline 99 Galegine 22 Erythratine 99 Ganglia 185, 187 Erythrina 99, 187 Gangliosides 185, 195, 202 Erythrinans 99 Garrya 1)5, 156 Erythroxylum 6, 58, 59 Garryine 157 coca 35,59 Geissoschizine 119-121, 123, 125 Escherichia coli 174 Gelsemine 121, 125 Eschscholtzia 99 Genetics 4,5, 17,43,68,72,100,160, Eschscholtzidine
Recommended publications
  • Aldrich FT-IR Collection Edition I Library
    Aldrich FT-IR Collection Edition I Library Library Listing – 10,505 spectra This library is the original FT-IR spectral collection from Aldrich. It includes a wide variety of pure chemical compounds found in the Aldrich Handbook of Fine Chemicals. The Aldrich Collection of FT-IR Spectra Edition I library contains spectra of 10,505 pure compounds and is a subset of the Aldrich Collection of FT-IR Spectra Edition II library. All spectra were acquired by Sigma-Aldrich Co. and were processed by Thermo Fisher Scientific. Eight smaller Aldrich Material Specific Sub-Libraries are also available. Aldrich FT-IR Collection Edition I Index Compound Name Index Compound Name 3515 ((1R)-(ENDO,ANTI))-(+)-3- 928 (+)-LIMONENE OXIDE, 97%, BROMOCAMPHOR-8- SULFONIC MIXTURE OF CIS AND TRANS ACID, AMMONIUM SALT 209 (+)-LONGIFOLENE, 98+% 1708 ((1R)-ENDO)-(+)-3- 2283 (+)-MURAMIC ACID HYDRATE, BROMOCAMPHOR, 98% 98% 3516 ((1S)-(ENDO,ANTI))-(-)-3- 2966 (+)-N,N'- BROMOCAMPHOR-8- SULFONIC DIALLYLTARTARDIAMIDE, 99+% ACID, AMMONIUM SALT 2976 (+)-N-ACETYLMURAMIC ACID, 644 ((1S)-ENDO)-(-)-BORNEOL, 99% 97% 9587 (+)-11ALPHA-HYDROXY-17ALPHA- 965 (+)-NOE-LACTOL DIMER, 99+% METHYLTESTOSTERONE 5127 (+)-P-BROMOTETRAMISOLE 9590 (+)-11ALPHA- OXALATE, 99% HYDROXYPROGESTERONE, 95% 661 (+)-P-MENTH-1-EN-9-OL, 97%, 9588 (+)-17-METHYLTESTOSTERONE, MIXTURE OF ISOMERS 99% 730 (+)-PERSEITOL 8681 (+)-2'-DEOXYURIDINE, 99+% 7913 (+)-PILOCARPINE 7591 (+)-2,3-O-ISOPROPYLIDENE-2,3- HYDROCHLORIDE, 99% DIHYDROXY- 1,4- 5844 (+)-RUTIN HYDRATE, 95% BIS(DIPHENYLPHOSPHINO)BUT 9571 (+)-STIGMASTANOL
    [Show full text]
  • “Biosynthesis of Morphine in Mammals”
    “Biosynthesis of Morphine in Mammals” D i s s e r t a t i o n zur Erlangung des akademischen Grades Doctor rerum naturalium (Dr. rer. nat.) vorgelegt der Naturwissenschaftlichen Fakultät I Biowissenschaften der Martin-Luther-Universität Halle-Wittenberg von Frau Nadja Grobe geb. am 21.08.1981 in Querfurt Gutachter /in 1. 2. 3. Halle (Saale), Table of Contents I INTRODUCTION ........................................................................................................1 II MATERIAL & METHODS ........................................................................................ 10 1 Animal Tissue ....................................................................................................... 10 2 Chemicals and Enzymes ....................................................................................... 10 3 Bacteria and Vectors ............................................................................................ 10 4 Instruments ........................................................................................................... 11 5 Synthesis ................................................................................................................ 12 5.1 Preparation of DOPAL from Epinephrine (according to DUNCAN 1975) ................. 12 5.2 Synthesis of (R)-Norlaudanosoline*HBr ................................................................. 12 5.3 Synthesis of [7D]-Salutaridinol and [7D]-epi-Salutaridinol ..................................... 13 6 Application Experiments .....................................................................................
    [Show full text]
  • S41467-019-09610-2.Pdf
    Corrected: Author correction ARTICLE https://doi.org/10.1038/s41467-019-09610-2 OPEN Mechanism-based tuning of insect 3,4-dihydroxyphenylacetaldehyde synthase for synthetic bioproduction of benzylisoquinoline alkaloids Christopher J. Vavricka1, Takanobu Yoshida1, Yuki Kuriya1, Shunsuke Takahashi 1, Teppei Ogawa2, Fumie Ono3, Kazuko Agari1, Hiromasa Kiyota4, Jianyong Li5, Jun Ishii 1, Kenji Tsuge1, Hiromichi Minami6, Michihiro Araki1,3, Tomohisa Hasunuma1,7 & Akihiko Kondo 1,7,8 1234567890():,; Previous studies have utilized monoamine oxidase (MAO) and L-3,4-dihydroxyphenylalanine decarboxylase (DDC) for microbe-based production of tetrahydropapaveroline (THP), a benzylisoquinoline alkaloid (BIA) precursor to opioid analgesics. In the current study, a phylogenetically distinct Bombyx mori 3,4-dihydroxyphenylacetaldehyde synthase (DHPAAS) is identified to bypass MAO and DDC for direct production of 3,4-dihydrox- yphenylacetaldehyde (DHPAA) from L-3,4-dihydroxyphenylalanine (L-DOPA). Structure- based enzyme engineering of DHPAAS results in bifunctional switching between aldehyde synthase and decarboxylase activities. Output of dopamine and DHPAA products is fine- tuned by engineered DHPAAS variants with Phe79Tyr, Tyr80Phe and Asn192His catalytic substitutions. Balance of dopamine and DHPAA products enables improved THP biosynthesis via a symmetrical pathway in Escherichia coli. Rationally engineered insect DHPAAS produces (R,S)-THP in a single enzyme system directly from L-DOPA both in vitro and in vivo, at higher yields than that of the wild-type enzyme. However, DHPAAS-mediated downstream BIA production requires further improvement. 1 Graduate School of Science, Technology and Innovation, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan. 2 Mitsui Knowledge Industry Co., Ltd. (MKI), 2-3-33 Nakanoshima, Kita-ku, Osaka 530-0005, Japan.
    [Show full text]
  • Redalyc.BIOSYNTHESIS of MORPHINE: IT´S IMPORTANCE IN
    Revista de la Facultad de Medicina ISSN: 2357-3848 [email protected] Universidad Nacional de Colombia Colombia Perea-Sasiaín, José BIOSYNTHESIS OF MORPHINE: IT´S IMPORTANCE IN PARKINSON DISEASE Revista de la Facultad de Medicina, vol. 56, núm. 2, 2008, pp. 161-189 Universidad Nacional de Colombia Bogotá, Colombia Disponible en: http://www.redalyc.org/articulo.oa?id=576363914009 Cómo citar el artículo Número completo Sistema de Información Científica Más información del artículo Red de Revistas Científicas de América Latina, el Caribe, España y Portugal Página de la revista en redalyc.org Proyecto académico sin fines de lucro, desarrollado bajo la iniciativa de acceso abierto 161 OPINIONES, DEBATES Y CONTROVERSIAS BIOSYNTHESIS OF MORPHINE: IT´S IMPORTANCE IN PARKINSON DISEASE Biosíntesis de la morfina: su importancia en la enfermedad de Parkinson Resumen Se presenta una panorámica tabulada y gráfica de los conocimientos actuales sobre la biosíntesis de la morfina tanto en Papaver somniferum como en los animales. Hacemos un análisis general de dos funciones principales de la morfina en el ser humano y de la importancia de aclarar su biosíntesis para establecer las etapas defectuosas en los enfermos parkinsonianos. Se admite que el daño de las neuronas melánicas de la sustancia negra se produce por neurotoxinas endógenas, metabolitos anormales por cantidad o calidad, resultantes del metabolismo secundario de la dopamina lo cual desencadena la enfermedad de Parkinson idiopática. Deben diseñarse pruebas funcionales que permitan identificar dichos metabolitos en las poblaciones de alto riesgo genético y correlacionarlos con los alelos presentes en ellas. Se concluye que para un diagnóstico preclínico de la enfermedad de Parkinson idiopático es necesario comparar los niveles de morfina proveniente del sistema nervioso central en la sangre de personas normales y en parkinsonianos antes de cualquier tratamiento.
    [Show full text]
  • Green Routes for the Production of Enantiopure Benzylisoquinoline Alkaloids
    International Journal of Molecular Sciences Review Green Routes for the Production of Enantiopure Benzylisoquinoline Alkaloids Francesca Ghirga 1, Alessandra Bonamore 2,*, Lorenzo Calisti 2, Ilaria D’Acquarica 3,* ID , Mattia Mori 1, Bruno Botta 3 ID , Alberto Boffi 2 and Alberto Macone 2,* ID 1 Center for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia, Viale Regina Elena 291, 00161 Rome, Italy; [email protected] (F.G.); [email protected] (M.M.) 2 Deaprtment of Biochemical Sciences “A.Rossi Fanelli”, Sapienza University of Rome, Pizzale Aldo Moro 5, 00185 Rome, Italy; [email protected] (L.C.); alberto.boffi@uniroma1.it (A.B.) 3 Department of Chemistry and Technology of Drugs, Sapienza University of Rome, Pizzale Aldo Moro 5, 00185 Rome, Italy; [email protected] * Correspondence: [email protected] (A.B.); [email protected] (I.D.); [email protected] (A.M.); Tel.: +39-06-49910813 (A.M.) Received: 6 November 2017; Accepted: 16 November 2017; Published: 20 November 2017 Abstract: Benzylisoquinoline alkaloids (BIAs) are among the most important plant secondary metabolites, in that they include a number of biologically active substances widely employed as pharmaceuticals. Isolation of BIAs from their natural sources is an expensive and time-consuming procedure as they accumulate in very low levels in plant. Moreover, total synthesis is challenging due to the presence of stereogenic centers. In view of these considerations, green and scalable methods for BIA synthesis using fully enzymatic approaches are getting more and more attention. The aim of this paper is to review fully enzymatic strategies for producing the benzylisoquinoline central precursor, (S)-norcoclaurine and its derivatives.
    [Show full text]
  • Tetrahydropapaveroline Production by Stepwise Fermentation Using
    OPEN (R,S)-Tetrahydropapaveroline SUBJECT AREAS: production by stepwise fermentation MICROBIOLOGY INDUSTRIAL MICROBIOLOGY using engineered Escherichia coli BIOTECHNOLOGY Akira Nakagawa1, Chiaki Matsuzaki1, Eitaro Matsumura1, Takashi Koyanagi1, Takane Katayama1, Kenji Yamamoto1, Fumihiko Sato2, Hidehiko Kumagai1 & Hiromichi Minami1 Received 2 July 2014 1 Research Institute for Bioresources and Biotechnology, Ishikawa Prefectural University, Nonoichi-shi, Ishikawa 921-8836, Japan, 2 Accepted Division of Integrated Life Science, Graduate School of Biostudies, Kyoto University, Oiwake-cho, Kitashirakawa, Sakyo-ku, Kyoto 29 September 2014 606-8502, Japan. Published 21 October 2014 Tetrahydropapaveroline (THP), a benzylisoquinoline alkaloid (BIA) found in diverse pharmaceutical compounds, is used as a starting material for the production of BIA. THP also has various neurobiological properties but is difficult to synthesize. Therefore, a simple method for THP production is desired. Recent studies have shown that microbes, especially bacteria, can serve as platforms for synthesizing these complex Correspondence and compounds; however, because bacteria lack organelles, the designed synthetic pathway cannot be requests for materials compartmentalized. Thus, the metabolic flow is frequently inhibited or disrupted by undesirable reactions. should be addressed to Indeed, in the first attempt to synthesize THP using a single strain of engineered Escherichia coli, the yield , m H.M. (minami@ was quite low ( 5 M), mainly because of the oxidation of THP by tyrosinase, an essential enzyme in our production system. To circumvent these problems, we constructed a stepwise (R,S)-THP production ishikawa-pu.ac.jp) system, in which the dopamine-producing step and the subsequent THP-producing step were separated. The yield of (R,S)-THP reached 1.0 mM (287 mg/L), the highest yielding BIA production method using a microbe reported to date.
    [Show full text]
  • Escherichia Coli As a Host for Metabolic Engineering
    Metabolic Engineering xxx (xxxx) xxx–xxx Contents lists available at ScienceDirect Metabolic Engineering journal homepage: www.elsevier.com/locate/meteng Escherichia coli as a host for metabolic engineering Sammy Pontrellia, Tsan-Yu Chiub, Ethan I. Lanc, Frederic Y.-H. Chena,b, Peiching Changd,e, ⁎ James C. Liaob, a Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, USA b Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan c Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan d Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan e Material and Chemical Research Laboratories, Industrial Technology Research Institute, Hsinchu, Taiwan ABSTRACT Over the past century, Escherichia coli has become one of the best studied organisms on earth. Features such as genetic tractability, favorable growth conditions, well characterized biochemistry and physiology, and avail- ability of versatile genetic manipulation tools make E. coli an ideal platform host for development of industrially viable productions. In this review, we discuss the physiological attributes of E. coli that are most relevant for metabolic engineering, as well as emerging techniques that enable efficient phenotype construction. Further, we summarize the large number of native and non-native products that have been synthesized by E. coli, and address some of the future challenges in broadening substrate range and fighting phage infection. 1. Introduction acids which has traditionally been produced from the natural producer Corynebacterium glutamicum (Gusyatiner et al., 2017). E. coli production Escherichia coli is a Gram-negative, facultative anaerobic bacterium of n-butanol has also been demonstrated to the level similar to that originally discovered in the human colon in 1885 by German bacter- produced in Clostridia (Shen et al., 2011; Ohtake et al., 2017).
    [Show full text]
  • Recent Advances in the Chemistry of Oripavine and Its Derivatives
    Advances in Bioscience and Biotechnology, 2014, 5, 704-717 Published Online July 2014 in SciRes. http://www.scirp.org/journal/abb http://dx.doi.org/10.4236/abb.2014.58084 Recent Advances in the Chemistry of Oripavine and Its Derivatives Sandor Hosztafi Institute of Pharmaceutical Chemistry, Semmelweis University, Budapest, Hungary Email: [email protected] Received 2 May 2014; revised 16 June 2014; accepted 12 July 2014 Copyright © 2014 by author and Scientific Research Publishing Inc. This work is licensed under the Creative Commons Attribution International License (CC BY). http://creativecommons.org/licenses/by/4.0/ Abstract Oripavine is the major alkaloid of Papaver orientale. It is an important intermediate in the bio- synthesis of morphine alkaloids. Recently, new Papaver somniferum strains have been developed which accumulate thebaine and oripavine, but not morphine and codeine. Therefore, the chemi- stry of oripavine has been studied intensively to synthesize opioid pharmaceuticals such as oxy- morphone, naloxone and buprenorphine. Keywords Papaver orientale, Papaver somniferum, Oripavine, Thebaine, Top1 Poppy 1. Introduction Thebaine an alkaloid present in 0.2% - 0.8% in opium and a major constituent (90% of total alkaloid content) in Papaver bracteatum (which is morphine free), possesses little utility medically for two reasons: (a) its lack of the depressant and analgesic properties common to other morphine alkaloids and (b) its expression of extreme toxicity and CNS stimulation. Oripavine is also a minor alkaloid of the opium poppy, but it is the main alkaloid of the oriental poppy Papaver orientale, which is a perennial flowering plant. The development of the top1 poppy was an important finding for the opium industry in Australia, because this poppy strain produces thebaine and oripavine, but not morphine or codeine.
    [Show full text]
  • A Yeast Platform for High-Level Synthesis of Tetrahydroisoquinoline Alkaloids
    ARTICLE https://doi.org/10.1038/s41467-020-17172-x OPEN A yeast platform for high-level synthesis of tetrahydroisoquinoline alkaloids Michael E. Pyne1,2, Kaspar Kevvai 1,2, Parbir S. Grewal 3, Lauren Narcross1,2, Brian Choi 3, ✉ Leanne Bourgeois1,2, John E. Dueber 4,5 & Vincent J. J. Martin 1,2 The tetrahydroisoquinoline (THIQ) moiety is a privileged substructure of many bioactive natural products and semi-synthetic analogs. Plants manufacture more than 3,000 THIQ 1234567890():,; alkaloids, including the opioids morphine and codeine. While microbial species have been engineered to synthesize a few compounds from the benzylisoquinoline alkaloid (BIA) family of THIQs, low product titers impede industrial viability and limit access to the full chemical space. Here we report a yeast THIQ platform by increasing production of the central BIA intermediate (S)-reticuline to 4.6 g L−1, a 57,000-fold improvement over our first-generation strain. We show that gains in BIA output coincide with the formation of several substituted THIQs derived from amino acid catabolism. We use these insights to repurpose the Ehrlich pathway and synthesize an array of THIQ structures. This work provides a blueprint for building diverse alkaloid scaffolds and enables the targeted overproduction of thousands of THIQ products, including natural and semi-synthetic opioids. 1 Department of Biology, Concordia University, Montréal, QC, Canada. 2 Centre for Applied Synthetic Biology, Concordia University, Montréal, QC, Canada. 3 Department of Chemical and Biomolecular Engineering, University of California, Berkeley, Berkeley, CA, USA. 4 Department of Bioengineering, University of California, Berkeley, Berkeley, CA, USA. 5 Biological Systems & Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
    [Show full text]
  • A Yeast Platform for High-Level Synthesis of Natural and Unnatural Tetrahydroisoquinoline Alkaloids
    bioRxiv preprint doi: https://doi.org/10.1101/863506; this version posted December 5, 2019. 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. A yeast platform for high-level synthesis of natural and unnatural tetrahydroisoquinoline alkaloids Michael E. Pyne a,b, Kaspar Kevvai a,b,*, Parbir S. Grewalc,*, Lauren Narcross a,b, Brian Choic, Leanne Bourgeois a,b, John E. Dueberd, & Vincent J. J. Martin a,b, a Department of Biology, Concordia University, Montréal, Québec, Canada b Centre for Applied Synthetic Biology, Concordia University, Montréal, Québec, Canada c Department of Chemical and Biomolecular Engineering, University of California, Berkeley, Berkeley, California, USA d Department of Bioengineering, University of California, Berkeley, Berkeley, California, USA * These authors contributed equally to this work Correspondence and requests for materials should be addressed to: Vincent J.J. Martin (email: [email protected]) bioRxiv preprint doi: https://doi.org/10.1101/863506; this version posted December 5, 2019. 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. ABSTRACT The tetrahydroisoquinoline (THIQ) moiety is a privileged substructure of many bioactive natural products and semi-synthetic analogues. The plant kingdom manufactures more than 3,000 THIQ alkaloids, including the opioids morphine and codeine.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2005/0043408A1 Yeboah Et Al
    US 2005.0043408A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2005/0043408A1 Yeboah et al. (43) Pub. Date: Feb. 24, 2005 (54) ANTI-GLYCATION AGENTS FOR Related U.S. Application Data PREVENTINGAGE- DIABETES- AND SMOKING-RELATED COMPLICATIONS (60) Provisional application No. 60/328,808, filed on Oct. 15, 2001. (76) Inventors: Faustinus Yeboah, Longueuil (CH); Publication Classification Yasuo Konishi, Kirkland (CA); Sung Ju Cho, Montreal (CA); Jittiwud (51) Int. Cl." ...................... A61K 31/195; CO7C 31/137 Lertvorachon, Montreal (CA); Taira (52) U.S. Cl. ........................... 514/567; 514/649; 514/651 Kiyota, St. Laurent (CA); Popek Tomasz, Pointe-Claire (CA) (57) ABSTRACT The invention provides new inhibitors of protein glycation, Correspondence Address: identified from compound libraries by a high throughput BORDEN LADNER GERVAS LLP Screening assay. The anti-glycation agents So identified are WORLD EXCHANGE PLAZA characterized by a variety of chemical Structures and are 100 QUEEN STREETSUITE 1100 useful for the prevention or treatment of age-, diabetes-, and OTTAWA, ON K1P 1J9 (CA) Smoking-related complications, including neuropathy, neph ropathy, ocular pathologies, or the loSS of mechanical prop erties of collagenous tissues. Among compounds identified (21) Appl. No.: 10/492,553 as having the anti-glycation activity, of Special interest are epinephrine and its analogs, in particular D-epinephrine and (22) PCT Filed: Oct. 15, 2002 its analogs, which are particularly useful for the prevention or treatment of age-, diabetes-, and Smoking-related ocular (86) PCT No.: PCT/CA02/01552 pathologies. Patent Application Publication Feb. 24, 2005 Sheet 1 of 2 US 2005/0043408 A1 100 L-Norepinephrine IC50=59 uM 8 O 60 | 4.O 2 O Log inhibitor FIG.
    [Show full text]
  • Urinary Excretion of Morphine and Biosynthetic Precursors in Mice
    Urinary excretion of morphine and biosynthetic precursors in mice Nadja Grobea,1, Marc Lamshöftb,1, Robert G. Orthc, Birgit Drägerd, Toni M. Kutchana, Meinhart H. Zenka,2,3, and Michael Spitellerb,2 aDonald Danforth Plant Science Center, 975 North Warson Road, St. Louis, MO 63132; bInstitute of Environmental Research, University of Technology Dortmund, Otto-Hahn-Strasse 6, 44227 Dortmund, Germany; cApis Discoveries LLC, 5827 Buffalo Ridge Road, P.O. Box 55, Gerald, MO 63037; and dInstitute of Pharmacy, Martin-Luther-University Halle-Wittenberg, Hoher Weg 8, 06120 Halle, Germany Contributed by Meinhart H. Zenk, March 17, 2010 (sent for review December 1, 2009) It has been firmly established that humans excrete a small but been reported in human and rodent brain tissue as well as in urine steady amount of the isoquinoline alkaloid morphine in their urine. (13, 16–22). This firmly established occurrence led in the past to It is unclear whether it is of dietary or endogenous origin. There is no speculations that THP might be the precursor of endogenous doubt that a simple isoquinoline alkaloid, tetrahydropapaveroline morphine. Experiments were not, however, conducted to test this (THP), is found in human and rodent brain as well as in human urine. hypothesis. We investigate here the formation of mammalian This suggests a potential biogenetic relationship between both morphine by analyzing the biosynthetic pathway at three points: alkaloids. Unlabeled THP or [1; 3; 4-D3]-THP was injected intraperito- first, the simple substituted metabolites formed by injection i.p. of neally into mice and the urine was analyzed. This potential precur- THP; second, the phenol-coupled products formed from reticu- 0 sor was extensively metabolized (96%).
    [Show full text]