DOCSLIB.ORG

WO 2017/050853 Al 30 March 2017 (30.03.2017) P O P C T

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
WO 2017/050853 Al 30 March 2017 (30.03.2017) P O P C T (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2017/050853 Al 30 March 2017 (30.03.2017) P O P C T (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every C12P 19/44 (2006.01) C12N 15/52 (2006.01) kind of national protection available): AE, AG, AL, AM, C12P 17/06 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, (21) Number: International Application DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, PCT/EP20 16/072474 HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, (22) International Filing Date: KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, 2 1 September 2016 (21 .09.201 6) MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, (25) Filing Language: English SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, (26) Publication Language: English TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: 62/222,919 24 September 2015 (24.09.2015) US (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, (71) Applicant: EVOLVA SA [CH/CH]; Duggingerstrasse 23, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, 4153 Reinach (CH). TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, (72) Inventors: NAESBY, Michael; 2, rue de l'hotel de ville, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, 68330 Huningue (FR). ZOKOURI, Zina; Schreinerstrasse LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, 43, 8004 Zurich (CH). FISCHER, David; Gotthelfweg 5, SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, 4144 Arlesheim (CH). EICHENBERGER, Michael; Gil- GW, KM, ML, MR, NE, SN, TD, TG). genbergerstrasse 23, 4053 Basel (CH). HANSSON, An¬ ders; Riehentorstrasse 33, 4058 Basel (CH). Published: (74) Agent: SMAGGASGALE, Gillian Helen; 138 Fetter — with international search report (Art. 21(3)) Lane, London EC4A 1BT (GB). — with sequence listing part of description (Rule 5.2(a)) (54) Title: PRODUCTION OF ANTHOCYANIN FROM SIMPLE SUGARS b) ∞ o o FIG. 1 (57) Abstract: Methods for producing anthocyanin by expression in a microorganism are disclosed including culturing of the mi o croorganism under anthocyanin producing conditions, wherein the microorgamsm has an operative metabolic pathway including at least one heterologous enzyme activity, the pathway producing anthocyanin from simple sugars or other simple carbon sources. PRODUCTION OF ANTHOCYANIN FROM SIMPLE SUGARS BACKGROUND OF THE INVENTION Field of the Invention [0001] Provided are methods for producing anthocyanins in recombinant host cells. Description of Related Art [0002] Over the last decade there have been several reports of heterologous production of flavonoids, including anthocyanins, using unicellular hosts, particularly in the prokaryote, Escherichia coli, and the eukaryote, Saccharomyces cerevisiae. Especially in E. coli there has been some success, predominantly after feeding intermediates of the flavonoid pathway to the bacteria. This has allowed several flavanones, flavones, and flavonols to be produced from phenyl propanoid precursors (see e.g., Yan 2005; Jiang 2005; Leonard 2007, respectively). In addition, several other flavonoids were made by intermediate feeding, such as isoflavonoids from liquiritigenin; flavan-3-ols and flavan-4-ols from flavanones; and anthocyanins from either flavanones or from (+)-catechin. However, there are no reports of anthocyanins being produced from basal medium components such as sugar or from the natural precursors phenylalanine or tyrosine. [0003] The anthocyanin biosynthetic pathway is shown n FIG. As shown, in this pathway the flavonoid intermediate coumaroyl-CoA is produced via the plant phenylpropanoid pathway. Phenylalanine is deaminated by the action of phenylalanine ammonia lyase (PAL), an enzyme of the ammonia lyase family, to form cinnamic acid. Cinnamic acid is then hydroxylated to p-coumaric acid (also called 4-coumaric acid) by cinnamate 4-hydroxylase (C4H), a CYP450 enzyme. Alternatively, p-coumaric acid is formed directly from tyrosine by the action of tyrosine ammonia lyase (TAL). Some enzymes have both PAL and TAL activity. The enzyme 4-coumarate-CoA-ligase (4CL) activates p-coumaric acid to p-coumaroyl CoA by attachment of a CoA group. [0004] Chalcone synthase (CHS), a polyketide synthase, is the first committed enzyme in the flavonoid pathway, and catalyzes synthesis of naringenin chalcone from one molecule of p-coumaroyl CoA and three molecules of malonyl CoA . Naringenin chalcone is rapidly and stereospecifically isomerized to the colorless (2S)-naringenin by chalcone isomerase (CHI). (2S)-Naringenin is hydroxylated at the 3-position by flavanone 3-hydroxylase (F3H) to yield (2R,3R)-dihydrokaempferol, a dihydroflavonol. F3H belongs to the 2-oxoglutarate-dependent dioxygenase (20DD) family. Flavonoid 3'-hydroxylase (F3'H) and flavonoid 3',5'-hydroxylase (F3'5'H), which are P450 enzymes, catalyze hydroxylation of dihydrokaempferol (DHK) to form (2R.3R)- dihydroquercetin and dihydromyricetin, respectively. F3'H and F3'5'H determine the hydroxylation pattern of the B-ring of flavonoids and anthocyanins and are necessary for cyanidin and delphinidin production, respectively. They are the key enzymes that determine the structures of anthocyanins and thus their color. Dihydroflavonols are reduced to corresponding 3,4-cis leucoanthocyanidins by the action of dihydroflavonol 4-reductase (DFR). Anthocyanidin synthase (ANS, also called leucoanthocyanidin dioxygenase or LDOX), which belongs to the 20DD family, catalyzes synthesis of corresponding colored anthocyanidins. In contrast to the well-conserved main pathway of flavonoid biosynthesis described above, modification of anthocyanidins is family- or species-dependent and can be very diverse. Additionally, in order to form more stable anthocyanins, anthocyanidins can be 3-glucosylated by the action of UDP- glucose:flavonoid (or anthocyanidin) 3GT. [0005] In yeast {e.g., S. cerevisiae), some of the same molecules (flavanones, flavones, and flavonols) have been made from phenyl propanoids. In addition, a few examples have been reported of production of flavonoids from sugar, e.g., naringenin (Koopman et al. 2012) and various flavanones and flavonols (Naesby 2009). However, production of anthocyanins has never been reported. [0006] Therefore, new approaches are required for producing anthocyanins via heterologous biosynthetic pathways in microbes. SUMMARY OF THE INVENTION [0007] It is against the above background that the present invention provides certain advantages and advancements over the prior art. Set forth herein are methods developed by selection of highly active heterologous genes, and by balancing the expression thereof, that produce anthocyanins from glucose in a microorganism host cell. Specifically provided herein are operative metabolic pathways for producing anthocyanins from glucose or other simple sugars. [0008] In a first aspect, the invention provides a microorganism including an operative metabolic pathway capable of producing an anthocyanin from glucose. The operative metabolic pathway includes at least a 4-coumaric acid-CoA ligase (4CL), a chalcone synthase (CHS), a flavanone 3-hydroxylase (F3H), a dihydroflavonol-4- reductase (DFR), an anthocyanidin synthase (ANS), an anthocyanidin 3-0- glycosyltransferase (A3GT), a chalcone isomerase (CHI), and at least one of a) a tyrosine ammonia lyase; or b) a phenylalanine ammonia lyase (PAL) and a trans- cinnamate 4-monooxygenase (C4H). At least one enzyme of the operative metabolic pathway is encoded by a gene heterologous to the microorganism is encoded by a gene heterologous to the microorganism. In particular embodiments, the anthocyanin is produced in a ratio of at least 1:1 to its anthocyanidin precursor by the operative metabolic pathway. [0009] In a second aspect, the invention provides a fermentation vessel including a microorganism having an operative metabolic pathway producing an anthocyanin from glucose. The operative metabolic pathway includes a 4-coumaric acid-CoA ligase (4CL), a chalcone synthase (CHS), a flavanone 3-hydroxylase (F3H), a dihydroflavonol- 4-reductase (DFR), an anthocyanidin synthase (ANS), an anthocyanidin 3-0- glycosyltransferase (A3GT), a chalcone isomerase (CHI), and a tyrosine ammonia lyase or a phenylalanine ammonia lyase (PAL) and a trans-cinnamate 4-monooxygenase (C4H), wherein at least one enzyme of the operative metabolic pathway is encoded by a gene heterologous to the microorganism. [0010] In a third aspect, the invention provides a microorganism including an operative metabolic pathway producing an anthocyanin from glucose. The operative metabolic pathway includes a 4-coumaric acid-CoA ligase (4CL) encoded by the nucleic acid sequence set forth in SEQ ID NO: , a chalcone synthase (CHS) encoded by the nucleic acid sequence set forth in SEQ ID NO: 2 1, a flavanone 3-hydroxylase (F3H) encoded by the nucleic acid sequence set forth in SEQ ID NO: 3, a dihydroflavonol-4- reductase (DFR) encoded by the nucleic acid sequence set forth in SEQ D NO: 5 or SEQ D NO: 7 , an anthocyanidin synthase (ANS) encoded by the nucleic acid sequence set forth in SEQ ID NO: 9, an anthocyanidin 3-O-glycosyltransferase (A3GT) encoded by the nucleic acid sequence set forth in SEQ ID NO: 11, a chalcone isomerase (CHI) encoded by the nucleic acid sequence set forth n SEQ ID NO: 13, and at least one of a) a tyrosine ammonia lyase (TAL) encoded by the nucleic acid sequence set forth in SEQ ID NO: 15 or b) a phenylalanine ammonia lyase (PAL) encoded by the nucleic acid sequence set forth in SEQ ID NO: 17 and a trans-cinnamate 4-monooxygenase (C4H) encoded by the nucleic acid sequence set forth in SEQ D NO: 19. [0011] In a fourth aspect, a microorganism includes an operative metabolic pathway capable of producing an anthocyanin from a simple sugar.
Load more

Recommended publications
  • Chemistry and Pharmacology of Kinkéliba (Combretum
    CHEMISTRY AND PHARMACOLOGY OF KINKÉLIBA (COMBRETUM MICRANTHUM), A WEST AFRICAN MEDICINAL PLANT By CARA RENAE WELCH A Dissertation submitted to the Graduate School-New Brunswick Rutgers, The State University of New Jersey in partial fulfillment of the requirements for the degree of Doctor of Philosophy Graduate Program in Medicinal Chemistry written under the direction of Dr. James E. Simon and approved by ______________________________ ______________________________ ______________________________ ______________________________ New Brunswick, New Jersey January, 2010 ABSTRACT OF THE DISSERTATION Chemistry and Pharmacology of Kinkéliba (Combretum micranthum), a West African Medicinal Plant by CARA RENAE WELCH Dissertation Director: James E. Simon Kinkéliba (Combretum micranthum, Fam. Combretaceae) is an undomesticated shrub species of western Africa and is one of the most popular traditional bush teas of Senegal. The herbal beverage is traditionally used for weight loss, digestion, as a diuretic and mild antibiotic, and to relieve pain. The fresh leaves are used to treat malarial fever. Leaf extracts, the most biologically active plant tissue relative to stem, bark and roots, were screened for antioxidant capacity, measuring the removal of a radical by UV/VIS spectrophotometry, anti-inflammatory activity, measuring inducible nitric oxide synthase (iNOS) in RAW 264.7 macrophage cells, and glucose-lowering activity, measuring phosphoenolpyruvate carboxykinase (PEPCK) mRNA expression in an H4IIE rat hepatoma cell line. Radical oxygen scavenging activity, or antioxidant capacity, was utilized for initially directing the fractionation; highlighted subfractions and isolated compounds were subsequently tested for anti-inflammatory and glucose-lowering activities. The ethyl acetate and n-butanol fractions of the crude leaf extract were fractionated leading to the isolation and identification of a number of polyphenolic ii compounds.
    [Show full text]
  • EEE M W 24B 24A 27B 27A N Patent Application Publication Dec
    US 2009031 1494A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2009/0311494 A1 YAMASHTA et al. (43) Pub. Date: Dec. 17, 2009 (54) RELIEF PRINTING PLATE PRECURSOR FOR (30) Foreign Application Priority Data LASER ENGRAVING, RELIEF PRINTING PLATE, AND PROCESS FOR PRODUCING Jun. 17, 2008 (JP) ................................. 2008-157907 RELEF PRINTING PLATE Feb. 10, 2009 (JP) ................................. 2009-028816 (75) Inventors: Masako YAMASHITA, Publication Classification Shizuoka-ken (JP); Atsushi (51) Int. Cl. SUGASAKI, Shizuoka-ken (JP) B32B 3/00 (2006.01) Correspondence Address: GO3F 7/20 (2006.01) Moss & Burke, PLLC GO3F 7/004 (2006.01) 401 Holland Lane, Suite 407 Alexandria, VA 22314 (US) (52) U.S. Cl. .................... 428/195.1: 430/306: 430/286.1 (73) Assignee: FUJIFILM CORPORATION, (57) ABSTRACT Tokyo (JP) A relief printing plate precursor for laser engraving, including (21) Appl. No.: 12/476,260 a relief forming layer containing (A) a polymerizable com pound having an ethylenic unsaturated bond. (B) a binder (22) Filed: Jun. 2, 2009 polymer, and (C) a compound having deodorizing ability. 11 50 FA - 42 SUB SCANNING DIRECTION -10 - 228 7.s 55 21B EEE m w 24B 24A 27B 27A N Patent Application Publication Dec. 17, 2009 US 2009/0311494 A1 F.G. 1 FA SCANNING DIRECTION 7OA a. CSy ra & 5A - 27WSNS AD 23Ar S3EEASEE21 E-25sagaa EEEEEEEEEEEEEEEEEEEEEEEEE-22s awslighlights fskillsw. 21B 2 TTT "TT". US 2009/031 1494 A1 Dec. 17, 2009 RELEF PRINTING PLATE PRECURSORFOR mask to develop and remove an uncured area, and there is LASER ENGRAVING, RELIEF PRINTING room for improvement since development treatment is nec PLATE, AND PROCESS FOR PRODUCING essary.
    [Show full text]
  • ABSTRACT YUZUAK, SEYIT. Utilizing Metabolomics and Model Systems
    ABSTRACT YUZUAK, SEYIT. Utilizing Metabolomics and Model Systems to Gain Insight into Precursors and Polymerization of Proanthocyanidins in Plants (Under the direction of Dr. De-Yu Xie). Proanthocyanidins (PAs) are oligomers or polymers of flavan-3-ols. In plants, PAs have multiple protective functions against biotic and abiotic stresses. PAs are also important nutraceuticals existing in common beverages and food products to benefit human health. To date, although the biosynthesis of PAs has been intensively studieed and fundamental progress has been made in over the past decades, many questions remain unanswered. For example, its direct precursors of extension units are unknown and their monomer structure diversity are also unclear. These questions about proanthocyanidins result from not having of model systems and effective technologies. Our laboratory has made significant progress in enhancing the understanding of these unknown and unclear points regarding proanthocyanidins. In my dissertation research reported here, I focus on two areas: testing muscadine as a crop system to develop metabolomics for studying precursor diversity and isolating enzymes from a red cell tobacco system to understand the precursors of the extension units of PA. First, I developed a metabolomics protocol to analyze anthocyanidins and anthocyanins in muscadine grape. This study demonstrated that muscadine berries can produce at least six anthocyanidins, revealing the diversity of pathway precursors for PAs. The Journal of Agriculture and Food Chemistry is reviewing this work. Second, I developed a metabolomics protocol of HPLC-qTOF-MS/MS to analyze flavan- 3-ols and dimeric PAs in muscadine grape. This study also demonstrated the high structure diversity of flavan-3-ols, particularly methylated flavan-3-ols.
    [Show full text]
  • Interactions with Microbial Proteins Driving the Antibacterial Activity of Flavonoids
    pharmaceutics Review Interactions with Microbial Proteins Driving the Antibacterial Activity of Flavonoids Giuliana Donadio 1,†, Francesca Mensitieri 2,†, Valentina Santoro 1, Valentina Parisi 1,3, Maria Laura Bellone 1,3, Nunziatina De Tommasi 1, Viviana Izzo 2 and Fabrizio Dal Piaz 2,* 1 Department of Pharmacy, University of Salerno, 84084 Fisciano, Italy; [email protected] (G.D.); [email protected] (V.S.); [email protected] (V.P.); [email protected] (M.L.B.); [email protected] (N.D.T.) 2 Department of Medicine and Surgery, University of Salerno, 84082 Baronissi, Italy; [email protected] (F.M.); [email protected] (V.I.) 3 PhD Program in Drug Discovery and Development, Department of Pharmacy, University of Salerno, 84084 Fisciano, Italy * Correspondence: [email protected] † These authors contributed equally to this work. Abstract: Flavonoids are among the most abundant natural bioactive compounds produced by plants. Many different activities have been reported for these secondary metabolites against numerous cells and systems. One of the most interesting is certainly the antimicrobial, which is stimulated through various molecular mechanisms. In fact, flavonoids are effective both in directly damaging the envelope of Gram-negative and Gram-positive bacteria but also by acting toward specific molecular targets essential for the survival of these microorganisms. The purpose of this paper is to present an overview of the most interesting results obtained in the research focused on the study of the Citation: Donadio, G.; Mensitieri, F.; interactions between flavonoids and bacterial proteins. Despite the great structural heterogeneity Santoro, V.; Parisi, V.; Bellone, M.L.; of these plant metabolites, it is interesting to observe that many flavonoids affect the same cellular De Tommasi, N.; Izzo, V.; Dal Piaz, F.
    [Show full text]
  • Purple Anthocyanin Colouration on Lower (Abaxial) Leaf Surface of Hemigraphis Colorata (Acanthaceae)
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by NORA - Norwegian Open Research Archives Phytochemistry 105 (2014) 141–146 Contents lists available at ScienceDirect Phytochemistry journal homepage: www.elsevier.com/locate/phytochem Purple anthocyanin colouration on lower (abaxial) leaf surface of Hemigraphis colorata (Acanthaceae) Irene Skaar a, Christopher Adaku b, Monica Jordheim a, Robert Byamukama b, Bernard Kiremire b, ⇑ Øyvind M. Andersen a, a Department of Chemistry, University of Bergen, Allégt. 41, 5007 Bergen, Norway b Chemistry Department, Makerere University, P.O. Box 7062, Kampala, Uganda article info abstract Article history: The functional significance of anthocyanin colouration of lower (abaxial) leaf surfaces is not clear. Received 1 August 2013 Two anthocyanins, 5-O-methylcyanidin 3-O-(300-(b-glucuronopyranosyl)-b-glucopyranoside) (1) and Received in revised form 19 May 2014 5-O-methylcyanidin 3-O-b-glucopyranoside (2), were isolated from Hemigraphis colorata (Blume) Available online 20 June 2014 (Acanthaceae) leaves with strong purple abaxial colouration (2.2 and 0.6 mg/g fr. wt., respectively). The glycosyl moiety of 1, the disaccharide 300-(b-glucuronopyranosyl)-b-glucopyranoside), has previously Keywords: been reported to occur only in a triterpenoid saponin, lindernioside A. The structural assignment of Hemigraphis colorata the aglycone of 1 and 2 is the first complete characterisation of a natural 7-hydroxy-5-methoxyanthocy- Acanthaceae anidin. Compared to nearly all naturally occurring anthocyanidins, the 5-O-methylation of this anthocy- Abaxial leaf colouration Anthocyanins anidin limits the type of possible quinoidal forms of 1 and 2 to be those forms with keto-function in only 0 5-O-Methylcyanidin their 7- and 4 -positions.
    [Show full text]
  • ABSTRACT ZENG, HAINIAN. Development
    ABSTRACT ZENG, HAINIAN. Development-dependent Formation and Metabolism of Anthocyanins and Proanthocyanidins in Acer Species. (Under the direction of David Danehower, William Hoffmann, Jenny Xiang and De-yu Xie). Anthocyanins are one of the richest pigments, which belong to flavonoid compounds in plant kingdom. They have many biological and ecological functions. Over the past many years, numerous efforts have been made to determine the biosynthetic pathway of anthocyanins and also to identify several regulatory proteins mainly in flowers and fruits of model plants and crop plants. However, many questions concerning the metabolism of anthocyanins in foliage remains unsolved. One example is “How can developmental processes impact on accumulation patterns of anthocyanins in leaves”. In this study, we choose several cultivars from one of the most popular ornamental plants Acer palmatum Thunb. to understand the mechanism of developmental changes of pigmentation in leaf. Several other maple species were also analyzed. We propose that the metabolism of anthocyanins play an essential role in such changes. We use an integrated approach of phytochemistry and metabolic profiling to determine the biosynthesis and metabolism of anthocyanins and their impacts on foliage color. Proanthocyanidin analysis was carried out as well to determine their relationship to both anthocyanin production and foliar coloration. We have found that even for green leaves with no/trace amount of detectable anthocyanins, the biosynthetic pathway of anthocyanidin/proanthocyanidin
    [Show full text]
  • Wo 2009/063333 A2
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date (10) International Publication Number 22 May 2009 (22.05.2009) PCT WO 2009/063333 A2 (51) International Patent Classification: Not classified (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, (21) International Application Number: AO, AT,AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, PCT/IB2008/003890 CH, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, (22) International Filing Date: IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, 14 November 2008 (14.1 1.2008) LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PG, PH, PL, PT, (25) Filing Language: English RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY,TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, (26) Publication Language: English ZW (84) Designated States (unless otherwise indicated, for every (30) Priority Data: kind of regional protection available): ARIPO (BW, GH, 60/987,866 14 November 2007 (14.1 1.2007) US GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, 61/037,191 17 March 2008 (17.03.2008) US ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), 12/270,23 1 13 November 2008 (13.11.2008) US European (AT,BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT,LU, LV,MC, MT, NL, (71) Applicant (for all designated States except US): OMNICA NO, PL, PT, RO, SE, SI, SK, TR), OAPI (BF, BJ, CF, CG, GMBH [DE/DE]; Plan 5, 20095 Hamburg (DE).
    [Show full text]
  • Ethnomedicinal Studies of Flora of Southern Punjab and Isolation of Biologically Active Principles
    ETHNOMEDICINAL STUDIES OF FLORA OF SOUTHERN PUNJAB AND ISOLATION OF BIOLOGICALLY ACTIVE PRINCIPLES DEPARTMENT OF CHEMISTRY LAHORE COLLEGE FOR WOMEN UNIVERSITY, LAHORE, PAKISTAN ETHNOMEDICINAL STUDIES OF FLORA OF SOUTHERN PUNJAB AND ISOLATION OF BIOLOGICALLY ACTIVE PRINCIPLES A THESIS SUBMITTED TO LAHORE COLLEGE FOR WOMEN UNIVERSITY, LAHORE IN THE PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY IN CHEMISTRY (PHYTO) By TAHIRA AZIZ MUGHAL DEPARTMENT OF CHEMISTRY LAHORE COLLEGE FOR WOMEN UNIVERSITY, LAHORE, PAKISTAN 2008 (i) DEPARTMENT OF CHEMISTRY LAHORE COLLEGE FOR WOMEN UNIVERSITY, LAHORE, PAKISTAN It is certified that the thesis entitled “Ethnomedicinal Studies of Floraof Southern Punjab and Isolation of Biologically Active Principles” submitted by Ms. Tahira Aziz Mughal to the Department of Chemistry, Lahore College for Women University, Lahore, PAKISTAN is her own work and is not submitted previously, in whole on in parts, in respect of any other academic award. Supervisor .............................................................................. Prof. Dr. Ismat Naeem Chairperson of the Department ...................................................................... Prof. Dr. Raskhshanda Nawaz (ii) ACKNOWLEDGEMENT First of all I bow my head before Almighty Allah with humble thanks that have enabled me to complete my research work. My all loves for Hazrat Mohammad (PBUH), a torch of guidance for all mankind for ever. My special gratitude goes to our ever active Vice Chancellor Prof Dr Bushra Mateen for providing me excellent research facilitations and patronage during the whole course of this research. I deem it a real privilege and source of pleasure to express my profound and cordial gratitude to my supervisor Prof Dr Ismat Naeem for her keen and continuous interest, ideas, suggestions, guidance, encouragement and support throughout the period of this research work.
    [Show full text]
  • The PLANT PHENOLIC COMPOUNDS Introduction & the Flavonoids the Plant Phenolic Compounds - 8,000 Phenolic Structures Known
    The PLANT PHENOLIC COMPOUNDS Introduction & The Flavonoids The plant phenolic compounds - 8,000 Phenolic structures known - Account for 40% of organic carbon circulating in the biosphere - Evolution of vascular plants: in cell wall structures, plant defense, features of woods and barks, flower color, flavors The plant phenolic compounds They can be: Simple, low molecular weight, single aromatic ringed compounds TO- Large and complex- polyphenols The Plant phenolic compounds The plant phenolic compounds - Primarily derived from the: Phenylpropanoid pathway and acetate pathway (and related pathways) Phenylpropanoid pathway and phenylpropanoid- acetate pathway Precursors for plant phenolic compounds The phenylpropanoids: products of the shikimic acid pathway The phenylpropanoids: products of the shikimic acid pathway (phe and tyr) THE PHENYLPROPANOIDS: PRODUCTS OF THE SHIKIMIC ACID PATHWAY (phe & tyr) The shikimate pathway The plant phenolic compounds - As in other cases of SMs, branches of pathway leading to biosynthesis of phenols are found or amplified only in specific plant families - Commonly found conjugated to sugars and organic acids The plant phenolic compounds Phenolics can be classified into 2 groups: 1. The FLAVONOIDS 2. The NON-FLAVONOIDS The plant phenolic compounds THE FLAVONOIDS - Polyphenolic compounds - Comprise: 15 carbons + 2 aromatic rings connected with a 3 carbon bridge The Flavane Nucleus THE FLAVONOIDS - Largest group of phenols: 4500 - Major role in plants: color, pathogens, light stress - Very often in epidermis of leaves and fruit skin - Potential health promoting compounds- antioxidants - A large number of genes known THE Flavonoids- classes Lepiniec et al., 2006 THE Flavonoids - The basic flavonoid skeleton can have a large number of substitutions on it: - Hydroxyl groups - Sugars - e.g.
    [Show full text]
  • Noid Subclasses on Treating Non-Small Cell Lung Carcinoma Associated with Cigarette Smoking
    Arya Rajendran et al /J. Pharm. Sci. & Res. Vol. 9(7), 2017, 1117-1121 Computational Simulation Studies of Various Flavo- noid Subclasses on Treating Non-Small Cell Lung Carcinoma Associated with Cigarette Smoking Arya Rajendran1, Shilpa Martin1, Reshma Eso1,Asha Ashokan2, Saranya T.S2* 1Student of B pharm ,Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, Amrita University, Kochi ,Kerala 2Department of Pharmaceutical Chemistry & Analysis, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, Amrita University,Kochi ,Kerala Abstract Lung cancer is one of the most prevailing cancers that cause death worldwide. Non-small cell lung cancer is getting tremen- dously increased day-by-day because of cigarette smoking. On exposure to the tobacco carcinogen- nicotine derived nitrosa- mine ketone (NNK) leads to the over expression of hepatocyte growth factor (HGF) and c-Met protein ,that triggers processes such as metastasis, angiogenesis, anti-apoptosis, enhanced cell growth and motility. Methotrexate treats NSCLC; with major side effects leucopenia and inflammation. So it was essential to propose a novel drug having more potential, least side effects and better therapeutic efficacy. The uptake of flavonoid foods can reduce the risk and further progression of lung cancer. Apart from antitumor activity, flavonoids also possess blood cell production and anti-inflammatory actions. Hence c-Met protein re- sides attractive binding sites for the invention of new drugs for NSCLC by the incorporation of computational simulation tools and softwares. The docking analysis was performed using Arguslab for the identification of best ligands by predicting the lig- and conformation in the protein active sites and assessment of binding affinities. Among 28 ligands were docked with the pro- tein (pdb id: 5EOB) all had shown higher docking scores than the standard drug methotrexate.
    [Show full text]
  • ABSTRACT Title of Dissertation / Thesis
    ABSTRACT Title of Dissertation / Thesis: ABSORPTION, EXCRETION, AND TRANSFORMATION OF INDIVIDUAL ANTHOCYANINS IN RATS Jian He, Master of Science, 2004 Dissertation / Thesis Directed By: Assistant Professor M. Monica Giusti Department of Nutr ition and Food Science Anthocyanins are poly phenolics responsible for most red to purple colors in plants. Human consumption is increasing because of their potential health benefits and use as natural colorants . However, their absorption and metabolism are not well characterized. We compared anthocyanin absorption and excretion in rats receiving chokeberry, bilberry or grape enriched diet (4g anthocyanin/kg) for 13 wee ks. Trace s of anthocyanins and metabolites were detected in plasma. In urine, intact an thocyanins and methylated derivatives ( ~ 24, 8, 1 5 mg cy -3-gla equivalent/L urine for chokeberry, bilberry, grape) were found. High metabolite concentration suggested accumulation of methylated anthocyanins in tissue. Fecal anthocyanin extraction was maxim ized with aqueous methanol (60%). Anthocyanin concentration in feces rang ed from 0.7 to 2g anthocyanin/kg, similar to cecal content. In the gut, anthocyanin degradation was high for glucosides, moderate for galactosides and negligible for arabinosides and xylosides . Both , glycosylation and acylation seemed to affect the bioavailability of anthocyanins in vivo . ABSORPTION, EXCRETION, AND TRANSFORMATION OF INDIVIDUAL ANTHOCYANINS IN RATS By Jian He Thesis submitted to the Faculty of th e Graduate School of the University of Maryland, College Park, in partial fulfillment of the requirements for the degree of Master of Science 2004 Advisory Committee: Assistant Professor M. Monica Giusti, Chair (Advisor) Assistant Professor Bern adene A. Magnuson (Co -advisor) Assistant Professor Liangli Yu © Copyright by Jian He 2004 Dedication The thesis is dedicated to my beloved father Shide He and mother Zonghui Hu, for supporting my education, and to my dear wife Weishu Xue, from whom the time devoted to this thesis has been withdrawn.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 8.449,927 B2 Eidenberger (45) Date of Patent: May 28, 2013
    USOO8449927B2 (12) United States Patent (10) Patent No.: US 8.449,927 B2 Eidenberger (45) Date of Patent: May 28, 2013 (54) STABILIZED ANTHOCYANN 5,912,363 A 6/1999 Nafisii-Movaghar et al. COMPOSITIONS 5,925,620 A 7/1999 Ohlenschlager et al. 6,171,602 B1 1/2001 Roman 6,569,446 B1 5/2003 Howard (75) Inventor: Thomas Eidenberger, Steyr (AT) 6,818,234 B1 1 1/2004 Nair et al. 7,820.207 B2 10/2010 Eidenberger (73) Assignee: Omnica GmbH, Hamburg (DE) 2001/0031744 A1 10, 2001 KOsbab 2002fOO18821 A1 2/2002 Soulier et al. Notice: Subject to any disclaimer, the term of this 2003/0027747 A1 2/2003 Yatcilla et al. (*) 2007/0O31517 A1 2/2007 Matar et al. patent is extended or adjusted under 35 2007/0082064 A1 4/2007 Krawitz U.S.C. 154(b) by 0 days. 2008/0255226 A1 10/2008 Eidenberger (21) Appl. No.: 13/442,455 FOREIGN PATENT DOCUMENTS EP 1474.999 4/2004 (22) Filed: Apr. 9, 2012 WO 92/03146 3, 1992 (65) Prior Publication Data OTHER PUBLICATIONS US 2012/0277173 A1 Nov. 1, 2012 Taulavuori et al., Plant Biol. 1, 1999, 187-191.* Maccarone, Emanuele et al., "Stabilization of Anthocyanins of Blood Related U.S. Application Data Orange Fruit Juice', vol. 50, (1985), Journal of Food Science, pp. 901-904, XP002516584. (63) Continuation of application No. 12/825,546, filed on Vaimakis V., et al., “Must oxygenation Together with Gluatathlone Jun. 29, 2010, now Pat. No. 8,153,168, which is a Addition in the Oxidation of WhiteWine.
    [Show full text]