DOCSLIB.ORG

( 12 ) United States Patent

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
( 12 ) United States Patent US010435673B2 (12 ) United States Patent ( 10 ) Patent No. : US 10 , 435 ,673 B2 Wessjohann et al. (45 ) Date of Patent : Oct. 8 , 2019 ( 54 ) METHOD FOR THE BIOTECHNOLOGICAL ( 56 ) References Cited PRODUCTION OF FLAVONOIDS (71 ) Applicant: Symrise AG , Holzminden (DE ) FOREIGN PATENT DOCUMENTS WO 2005 /084305 AL 9 /2005 (72 ) Inventors: Ludger Wessjohann , Halle (DE ) ; WO 2005 / 115377 Al 12 / 2005 Anne - Kathrin Bauer , Halle (DE ) ; Jakob Ley , Holzminden (DE ) ; Torsten OTHER PUBLICATIONS Geissler , Einbeck (DE ) ; Katrin Lee at al , “ Biotransformation of Flavonoids with O -Methyltransferase Geissler , Einbeck (DE ) from Bacillus cereus, " J . Microbiol. Biotechnol . (2008 ) , 16 ( 7 ) , pp . 1090 - 1096 ( 73 ) Assignee : SYMRISE AG , Holzminden (DE ) Kitamura et al, “ Production of Hydroxlated Flavonoids with Cytochrome P450 BM3 Variant F87V and Their Antioxidative Activities ,” Biosci . Biotechnol . Biochem . 77 (6 ) , pp . 1340 - 1343 (2013 ) . ( * ) Notice: Subject to any disclaimer, the term of this Wessjohann et al, “ Alkylating enzymes, ” Current Opinion in Chemi patent is extended or adjusted under 35 cal Biology 2013 , 17 :229 - 235 . U . S .C . 154 (b ) by 87 days. Kasai et al, “ Enzymatic properties of cytochrome P450 catalyzing 3 ' -hydroxylation of naringenin from the white- rot fungus Phanerochaete chrysosporium ,” Biochemical and Biophysical Research Commu (21 ) Appl. No. : 15 /514 , 120 nications 387 (2009 ), pp . 103 - 108 . Kabumoto et al, “ Directed Evolution of the Actinomycete Cytochrome ( 22 ) PCT Filed : Sep . 27 , 2015 P450 MOXA (CYP105 ) for Enhanced Activity , ” Biosci. Biotechnol . Biochem . 73 ( 9 ) , pp . 1922 - 1927 ( 2009 ) . European Search Report dated May 19 , 2015 in corresponding ( 86 ) PCT No .: PCT/ EP2015 /072189 European Application No . 14187583 . 1 . $ 371 ( c ) ( 1 ) , First Examination Report dated Dec . 22 , 2017 in corresponding European Application No . 14187583 . 1 . ( 2 ) Date : Mar. 24 , 2017 Bhuiya , M ., et al . , “ Engineering Monolignol 4 - 0 -Methyltransferases to Modulate Lignin Biosynthesis ,” Journal of Biological Chemistry , (87 ) PCT Pub . No .: WO2016 / 050656 vol . 285, No . 1 , pp . 277 - 285 ( Jan . 1 , 2010 ) . PCT Pub . Date : Apr . 7 , 2016 Ravichandran , K ., et al ., “ Crystal Structure of Hemoprotein Domain of P450BM - 3 , a Prototype for Microsomal P450 ' s , ” Science, vol . 261 , pp . 731 -736 ( Aug . 6 , 1993 ) . (65 ) Prior Publication Data Wils , C . , et al ., “ A Single Amino Acid Determines Position Speci ficity of an Arabidopsis thaliana CCOAOMT- like O -methyltransferase ." US 2018 / 0135029 A1 May 17 , 2018 FEBS Letters , vol. 587 , pp . 683 -689 (Feb . 14 , 2013 — on - line ) . (30 ) Foreign Application Priority Data Primary Examiner - Jennifer E Graser (74 ) Attorney , Agent, or Firm — Polsinelli PC Oct. 3 , 2014 (EP ) .. .. .. 14187583 (57 ) ABSTRACT A method is proposed for producing flavonoids , comprising (51 ) Int. Ci. the steps: (a ) providing of a transgenic microorganism , C12P 17 /06 ( 2006 .01 ) containing ( i ) a first nucleic acid section ( A ) , comprising or C12N 9 / 10 ( 2006 .01 ) consisting of a gene coding for a CYP450 oxidase , ( ii ) a CI2N 9 /02 ( 2006 . 01 ) second nucleic acid section ( B ), comprising or consisting of C12N 15 /64 ( 2006 .01 ) a gene coding for a plant O -methyltransferase , and ( b ) ( 52 ) U .S . CI. adding of one or more flavanones to the transgenic micro CPC . .. C12N 9 / 1007 (2013 . 01 ) ; C12N 9 /0071 organism , ( c ) the conversion of the substrate flavanones by ( 2013 .01 ) ; C12N 15 /64 ( 2013 . 01 ) ; C12P 17 / 06 the transgenic microorganism to the corresponding fla ( 2013 .01 ) ; C12Y 114 / 14001 ( 2013 .01 ) ; C12Y vonoids, and optionally ( d ) isolating and purifying of the 201/ 01 ( 2013 . 01 ) final products . ( 58 ) Field of Classification Search None 6 Claims, 8 Drawing Sheets See application file for complete search history . Specification includes a Sequence Listing . atent Oct. 8 , 2019 Sheet 1 of 8 US 10 ,435 ,673 B2 2000 CYP450 -Oxiclase pSYM _ BM3 8 ,519 bp Figure 1 Plasmid pSYM _ BM3 with CYP450 oxidase gene atent Oct. 8 , 2019 Sheet 2 of 8 US 10 ,435 ,673 B2 4,900 3.$ 90 2000 Sob MCPFOMT 'zo40 wito M 4 , 142 bp TTP H al z000 ' Figure 2 Plasmid pSYM _ PFOMT gene coding for O -methyltransferase atent Oct. 8 , 2019 Sheet 3 of 8 US 10 ,435 ,673 B2 . 600 800 .. 4,400 4 ,517 1,009 AtCOMTCO wat !OOV 4,000 PSYM _ ADCOMT code 4 , 517 bp noo olto M Octe 00bc 0092 Figure 3 PlasmidFigure pSYMPSY __ AtCOMTAICOMT genegene coding for cation - independent O -methyltransferase atent Oct. 8 , 2019 Sheet 4 of 8 US 10 ,435 ,673 B2 100 Substanceconcentration(%) 0 200 400 800 900 1000 1200 1400 1600 Incubation time (min ) eriodictyot - 0 . naringenin Figure 4 Biocatalytic transformation from naringenin to eriodictyol U . S . Patent Oct. 8 , 2019 Sheet 5 of 8 US 10 ,435 ,673 B2 120 * . ! Substanceconcentration(%) * . * * 0 20wwwwwwwwwwwwwwwwwwwwwwwwwwwwww 40 60bangsa wwwwwwwwwwwwwali80 WWWWWW 100 120 Incubation time ( s ) - Moeodictyo - 0 . eriodictyok Figure 5 Biocatalytic transformation from eriodictyol to homoeriodictyol BM3 [GVQC ) /PFOMT * Naringenin 49 . .. .. www friodictyol Range/106 Homoeriodictyol 1.4 . hennarration through there t hecharged pidid 25 Time ( s ) Figure 6 Fermentative transformation from naringenin to homoeriodictyol U .S . Patentatent Oct. 8 , 2019 Sheet 6 of 8 US 10 ,435 ,673 B2 . ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' 8M3 [GVQC ) /PFOMT + Eriodictyol Naringenin * Eriodictyol Range/106 « Homoeriodictyol 22 III 5 10 15 20 25 Time ( h ) Figure 7 Fermentative transformation from eriodictyol to homoeriodictyol BM3( GVQC ) + Naringenin - Naringenin Eriodictyol Range/106 O Homoeriodictyol EEEEEEEEEEEEEEEEEEEEEEEEEEEEEEEEE . ". ' . ' . ' . ' .' . ". 1 . 1 . 1 . 1 .1 . 1 . 1 . 1 . 1 . 1 .1 . 1 . 1 . 1 . 1 . 1 .1 . 1 . 1 . 1 . 1 . 1 .1 . 1. ' . ' . ' . ' .' . ". ' . ' . ' . " . 5 10 15 20 TIME (MY Figure 8 Fermentative transformation from naringenin to eriodictyol U . S . Patent Oct . 8 , 2019 Sheet 7 of 8 US 10 , 435 ,673 B2 M inin Figure 9 Isolation of CYP450 oxidase BM3 eeeeeeee Figure 10 Isolation of O -methyltransferase POMT Figure 11 Isolation of O -methyltransferase AtCOMT atent Oct. 8 , 2019 Sheet 8 of 8 US 10 ,435 ,673 B2 : : Substance(%) : . : :. : : : : : : : : GV VQ V GVQS GVQ BM3 variant . naringenin (Substrat ) M eriodictyol w apigenin Figure 12 Comparison of product formation of various variants of BM3 US 10 , 435 ,673 B2 METHOD FOR THE BIOTECHNOLOGICAL FIG . 6 shows the fermentative transformation from nar PRODUCTION OF FLAVONOIDS ingenin to homoeriodictyol; FIG . 7 shows the fermentative transformation from erio FIELD OF THE INVENTION dictyol to homoeriodictyol; 5 FIG . 8 shows the fermentative transformation from narin The invention is in the field of biotechnology and relates qenin to eriodictyol; to a process in which flavanone is converted to the corre FIG . 9 shows the isolation of CYP450 oxidase BM3; sponding flavonoids without requiring any intermediate FIG . 10 shows isolation of O -methyltransferase PfOMT; chemical steps , a corresponding microorganism , a vector , FIG . 11 shows isolation of O -methyltransferase AtCOMT; and a host cell . and STATE OF THE ART FIG . 12 compares product formation of various variants of BM3. Flavonoids such as , for example, homoeriodictyol, erio dictyol ( EP 1258200 B1) and hesperetin ( EP 1998636 B1) 15 DESCRIPTION OF THE INVENTION represent important flavouring and aroma substances . These substances are usually produced by an aldol reaction of free A first subject -matter of the invention relates to a process or partially methylated acetophloroglucinol with free or for the production of flavonoids, comprising the following partially methlylated protocatechualdehyde . Although the steps : processes have been established on an industrial scale , they 20 ( a ) Providing a transgenic microorganism , comprising exhibit significant disadvantages : during the course of reac tion it is necessary to provide the phenolic functions with ( i ) A first nucleic acid fragment ( A ), comprising or protective groups which need to be removed at a later point consisting of a gene coding for a CYP450 oxidase , in time. As a result , the syntheses become multi - stage , i. e . ( ii ) A second nucleic acid fragment ( B ) , comprising or technically complex and obviously also costly . 25 consisting of a gene coding for a plant O -methyltrans The subject matter of WO 2005 115377 A1 is a food ferase, and composition . comprising flavonoids and tocotrienol. ( b ) Adding one or more flavanones to the transgenic micro wherein the flavonoids may represent naringenin , hesperi organism , din , nobiletin or tangeretin . ( c ) Converting the flavanones contained in the substrate by However , it is particularly disadvantageous that these are 30 the transgenic microorganism to the corresponding fla chemical methods of production , i. e . for regulatory reasons vonoids , and , optionally the food additives , flavouring substances and aromas so ( d ) Isolating and purifying the final products . produced may not be designated as natural . However , a Surprisingly , it was found that by insertion of two differ designation as natural or nature - identical is crucial for many ent nucleic acid fragments , which contain a gene coding for consumers when making their purchase decision ; it is , 35 a bacterial CYP450 oxidase on the one hand and a gene therefore , obvious that there is a particular demand for coding for a plant
Load more

Recommended publications
  • Metabolomics Reveals the Molecular Mechanisms of Copper Induced
    Article Cite This: Environ. Sci. Technol. 2018, 52, 7092−7100 pubs.acs.org/est Metabolomics Reveals the Molecular Mechanisms of Copper Induced Cucumber Leaf (Cucumis sativus) Senescence † ‡ § ∥ ∥ ∥ Lijuan Zhao, Yuxiong Huang, , Kelly Paglia, Arpana Vaniya, Benjamin Wancewicz, ‡ § and Arturo A. Keller*, , † Key Laboratory of Pollution Control and Resource Reuse, School of Environment, Nanjing University, Nanjing, Jiangsu 210023, China ‡ Bren School of Environmental Science & Management, University of California, Santa Barbara, California 93106-5131, United States § University of California, Center for Environmental Implications of Nanotechnology, Santa Barbara, California 93106, United States ∥ UC Davis Genome Center-Metabolomics, University of California Davis, 451 Health Sciences Drive, Davis, California 95616, United States *S Supporting Information ABSTRACT: Excess copper may disturb plant photosynthesis and induce leaf senescence. The underlying toxicity mechanism is not well understood. Here, 3-week-old cucumber plants were foliar exposed to different copper concentrations (10, 100, and 500 mg/L) for a final dose of 0.21, 2.1, and 10 mg/plant, using CuSO4 as the Cu ion source for 7 days, three times per day. Metabolomics quantified 149 primary and 79 secondary metabolites. A number of intermediates of the tricarboxylic acid (TCA) cycle were significantly down-regulated 1.4−2.4 fold, indicating a perturbed carbohy- drate metabolism. Ascorbate and aldarate metabolism and shikimate- phenylpropanoid biosynthesis (antioxidant and defense related pathways) were perturbed by excess copper. These metabolic responses occur even at the lowest copper dose considered although no phenotype changes were observed at this dose. High copper dose resulted in a 2-fold increase in phytol, a degradation product of chlorophyll.
    [Show full text]
  • Studies of the Effects of Flavonoids on Roentgen Irradiation Disease
    STUDIES OF THE EFFECTS OF FLAVONOIDS ON ROENTGEN IRRADIATION DISEASE. II. COMPARISON OF THE PROTECTIVE INFLUENCE OF SOME FLAVONOIDS AND VITAMIN C IN DOGS John B. Field, Paul E. Rekers J Clin Invest. 1949;28(4):746-751. https://doi.org/10.1172/JCI102127. Research Article Find the latest version: https://jci.me/102127/pdf STUDIES OF THE EFFECTS OF FLAVONOIDS ON ROENTGEN IRRADIATION DISEASE. II. COMPARISON OF THE PROTECTIVE INFLUENCE OF SOME FLAVONOIDS AND VITAMIN C IN DOGS' By JOHN B. FIELD 2 AND PAUL E. REKERS (From the Department of Radiation Biology, University of Rochester, School of Medicine and Dentistry, Rochester, New York) (Received for publication February 22, 1949) The nature of dietary factors contributing to Thus, it has been proposed that rutin either de- the maintenance of vascular integrity has not, creases the rate of vascular disintegration, or in- as yet, been satisfactorily elucidated. However, creases its repair (12). vitamin C appears to play a specific role (1-3) by The purpose of this report is to summarize functioning in some manner to incorporate the vas- briefly observations on the activity of other sub- cular cement substance. The significance of other stances of the flavonoid and related groups and agents in alleviating "vascular purpura" has re- to indicate the relationship of these substances mained inconclusive. with vitamin C in the irradiated dog. It has been claimed that "vascular permeability" is dependent upon regulation by the entire class of METHODS "vitamin P" substances. Since 1936, the experi- Dogs of the beagle strain, identical to those utilized in mental device of eliminating "vitamin P" from the the previous study (12) were used throughout.
    [Show full text]
  • European Patent Office of Opposition to That Patent, in Accordance with the Implementing Regulations
    (19) TZZ _¥_T (11) EP 2 791 366 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: C12R 1/01 (2006.01) A01H 3/00 (2006.01) 26.04.2017 Bulletin 2017/17 (86) International application number: (21) Application number: 12805902.9 PCT/US2012/070036 (22) Date of filing: 17.12.2012 (87) International publication number: WO 2013/090884 (20.06.2013 Gazette 2013/25) (54) BRADYRHIZOBIUM STRAINS BRADYRHIZOBIUM STÄMME SOUCHES DE BRADYRHIZOBIUM (84) Designated Contracting States: • SUGAWARA MASAYUKI ET AL: "Functional Role AL AT BE BG CH CY CZ DE DK EE ES FI FR GB of Bradyrhizobium japonicum Trehalose GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO Biosynthesis and Metabolism Genes during PL PT RO RS SE SI SK SM TR Physiological Stress and Nodulation", APPLIED ANDENVIRONMENTAL MICROBIOLOGY, vol. 76, (30) Priority: 16.12.2011 US 201161576470 P no. 4, February 2010 (2010-02), pages 1071-1081, XP002694519, (43) Date of publication of application: • STREETER J G: "Effect of trehalose on survival 22.10.2014 Bulletin 2014/43 of Bradyrhizobium japonicum during desiccation.", JOURNAL OF APPLIED (73) Proprietors: MICROBIOLOGY 2003, vol. 95, no. 3, 2003, pages • Novozymes Bioag A/S 484-491, XP002694520, ISSN: 1364-5072 2880 Bagsvaerd (DK) • CYTRYN EDDIE J ET AL: "Transcriptional and • Novozymes Biologicals, Inc. physiological responses of Bradyrhizobium Salem, VA 24153 (US) japonicum to desiccation-induced stress.", JOURNAL OF BACTERIOLOGY OCT 2007, vol. (72) Inventors: 189, no. 19, October 2007 (2007-10), pages • KANG, Yaowei 6751-6762, XP002694521, ISSN: 0021-9193 Christiansburg, VA 24073 (US) • MARY P ET AL: "Differences among Rhizobium • TRAN, Anh melilotiand Bradyrhizobium japonicum strains in Roanoke, VA 24019 (US) tolerance to desiccation and storage at different • SEMONES, Shawn relative humidities", SOIL BIOLOGY AND Salem, VA 24153 (US) BIOCHEMISTRY,PERGAMON, OXFORD,GB, vol.
    [Show full text]
  • GRAS Notice (GRN) No.901, Glucosyl Hesperidin
    GRAS Notice (GRN) No. 901 https://www.fda.gov/food/generally-recognized-safe-gras/gras-notice-inventory ~~~lECTV!~ITJ) DEC 1 2 20,9 OFFICE OF FOOD ADDITI\/c SAFETY tnC Vanguard Regulator~ Services, Inc 1311 Iris Circle Broomfield, CO, 80020, USA Office: + 1-303--464-8636 Mobile: +1-720-989-4590 Email: [email protected] December 15, 2019 Dennis M. Keefe, PhD, Director, Office of Food Additive Safety HFS-200 Food and Drug Administration 5100 Paint Branch Pkwy College Park, MD 20740-3835 Re: GRAS Notice for Glucosyl Hesperidin Dear Dr. Keefe: The attached GRAS Notification is submitted on behalf of the Notifier, Hayashibara Co., ltd. of Okayama, Japan, for Glucosyl Hesperidin (GH). GH is a hesperidin molecule modified by enzymatic addition of a glucose molecule. It is intended for use as a general food ingredient, in food. The document provides a review of the information related to the intended uses, manufacturing and safety of GH. Hayashibara Co., ltd. (Hayashibara) has concluded that GH is generally recognized as safe (GRAS) based on scientific procedures under 21 CFR 170.30(b) and conforms to the proposed rule published in the Federal Register at Vol. 62, No. 74 on April 17, 1997. The publically available data and information upon which a conclusion of GRAS was made has been evaluated by a panel of experts who are qualified by scientific training and experience to assess the safety of GH under the conditions of its intended use in food. A copy of the Expert Panel's letter is attached to this GRAS Notice.
    [Show full text]
  • Everything Added to Food in the United States (EAFUS)
    Everything Added to Food in the United States (EAFUS) A to Z Index Follow FDA FDA Voice Blog Most Popular Searches Home Food Drugs Medical Devices Radiation-Emitting Products Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products Everything Added to Food in the United States (EAFUS) FDA Home Everything Added to Food in the United States (EAFUS) Everything Added to Food in the United States (EAFUS) - The list below is an alphabetical inventory representing only five of 196 fields in FDA/CFSAN's PAFA database. Definitions of the labels that are found in the inventory are: Label Definition DOCTYPE An indicator of the status of the toxicology information available for the substance in PAFA (administrative and chemical information is available on all substances): A Fully up-to-date toxicology information has been sought. S P E There is reported use of the substance, but it has not yet been assigned for toxicology literature search. A F N There is reported use of the substance, and an initial toxicology literature search is in progress. E W NI Although listed as a added to food, there is no current reported use of the substance, and, therefore, L although toxicology information may be available in PAFA, it is not being updated. N There is no reported use of the substance and there is no toxicology information available in PAFA. U L B The substance was formerly approved as a food additive but is now banned; there may be some toxicology A data available. N DOCNUM PAFA database number of the Food Additive Safety Profile volume containing the printed source information concerning the substance.
    [Show full text]
  • Evaluation of Anticancer Activities of Phenolic Compounds In
    EVALUATION OF ANTICANCER ACTIVITIES OF PHENOLIC COMPOUNDS IN BLUEBERRIES AND MUSCADINE GRAPES by WEIGUANG YI (Under the Direction of CASIMIR C. AKOH) ABSTRACT Research has shown that diets rich in phenolic compounds may be associated with lower risk of several chronic diseases including cancer. This study systematically evaluated the bioactivities of phenolic compounds in blueberries and muscadine grapes, and assessed their potential cell growth inhibition and apoptosis induction effects using two colon cancer cell lines (HT-29 and Caco-2), and one liver cancer cell line (HepG2). In addition, the absorption of blueberry anthocyanin extracts was evaluated using Caco-2 human intestinal cell monolayers. Polyphenols in three blueberry cultivars (Briteblue, Tifblue and Powderblue), and four cultivars of muscadine (Carlos, Ison, Noble, and Supreme) were extracted and freeze dried. The extracts were further separated into phenolic acids, tannins, flavonols, and anthocyanins using a HLB cartridge and LH20 column. In both blueberries and muscadine grapes, some individual phenolic acids and flavonoids were identified by HPLC with more than 90% purity in anthocyanin fractions. The dried extracts and fractions were added to the cell culture medium to test for cell growth inhibition and induction of apoptosis. Polyphenols from both blueberries and muscadine grapes had significant inhibitory effects on cancer cell growth. The phenolic acid fraction showed relatively lower bioactivities with 50% inhibition at 0.5-3 µg/mL. The intermediate bioactivities were observed in the flavonol and tannin fractions. The greatest inhibitory effect among all four fractions was from the anthocyanin fractions in the three cell lines. Cell growth was significantly inhibited more than 50% by the anthocyanin fractions at concentrations of 15-300 µg/mL.
    [Show full text]
  • Analysis of the Binding and Interaction Patterns of 100 Flavonoids with the Pneumococcal Virulent Protein Pneumolysin: an in Silico Virtual Screening Approach
    Available online a t www.scholarsresearchlibrary.com Scholars Research Library Der Pharmacia Lettre, 2016, 8 (16):40-51 (http://scholarsresearchlibrary.com/archive.html) ISSN 0975-5071 USA CODEN: DPLEB4 Analysis of the binding and interaction patterns of 100 flavonoids with the Pneumococcal virulent protein pneumolysin: An in silico virtual screening approach Udhaya Lavinya B., Manisha P., Sangeetha N., Premkumar N., Asha Devi S., Gunaseelan D. and Sabina E. P.* 1School of Biosciences and Technology, VIT University, Vellore - 632014, Tamilnadu, India 2Department of Computer Science, College of Computer Science & Information Systems, JAZAN University, JAZAN-82822-6694, Kingdom of Saudi Arabia. _____________________________________________________________________________________________ ABSTRACT Pneumococcal infection is one of the major causes of morbidity and mortality among children below 2 years of age in under-developed countries. Current study involves the screening and identification of potent inhibitors of the pneumococcal virulence factor pneumolysin. About 100 flavonoids were chosen from scientific literature and docked with pnuemolysin (PDB Id.: 4QQA) using Patch Dockprogram for molecular docking. The results obtained were analysed and the docked structures visualized using LigPlus software. It was found that flavonoids amurensin, diosmin, robinin, rutin, sophoroflavonoloside, spiraeoside and icariin had hydrogen bond interactions with the receptor protein pneumolysin (4QQA). Among others, robinin had the highest score (7710) revealing that it had the best geometrical fit to the receptor molecule forming 12 hydrogen bonds ranging from 0.8-3.3 Å. Keywords : Pneumococci, pneumolysin, flavonoids, antimicrobial, virtual screening _____________________________________________________________________________________________ INTRODUCTION Streptococcus pneumoniae is a gram positive pathogenic bacterium causing opportunistic infections that may be life-threating[1]. Pneumococcus is the causative agent of pneumonia and is the most common agent causing meningitis.
    [Show full text]
  • Interpretive Guide
    INTERPRETIVE GUIDE Contents INTRODUCTION .........................................................................1 NUTREVAL BIOMARKERS ...........................................................5 Metabolic Analysis Markers ....................................................5 Malabsorption and Dysbiosis Markers .....................................5 Cellular Energy & Mitochondrial Metabolites ..........................6 Neurotransmitter Metabolites ...............................................8 Vitamin Markers ....................................................................9 Toxin & Detoxification Markers ..............................................9 Amino Acids ..........................................................................10 Essential and Metabolic Fatty Acids .........................................13 Cardiovascular Risk ................................................................15 Oxidative Stress Markers ........................................................16 Elemental Markers ................................................................17 Toxic Elements .......................................................................18 INTERPRETATION-AT-A-GLANCE .................................................19 REFERENCES .............................................................................23 INTRODUCTION A shortage of any nutrient can lead to biochemical NutrEval profile evaluates several important biochemical disturbances that affect healthy cellular and tissue pathways to help determine nutrient
    [Show full text]
  • Note Preparation of a Lemon Flavonoid Aglycone and Its
    Food Sci. Technol. Res., 15 (1), 83–88, 2009 Note Preparation of a Lemon Flavonoid Aglycone and its Suppressive Effect on the Susceptibility of LDL to Oxidation Following Human Ingestion 1* 2 2 3 2 Yoshiaki MIYAKE , Chika SAKURAI , Mika USUDA , Masanori HIRAMITSU and Kazuo KONDO 1 Faculty of Human Wellness, Tokaigakuen University, Nagoya 468-8514, Japan 2 Institute of Environmental Science for Human Life, Ochanomizu University, Tokyo 112-8610, Japan 3 Pokka Corporation Ltd., Kitanagoya City, Aichi 481-8515, Japan Received July 4, 2008; Accepted September 5, 2008 Lemon flavonoid (LF) prepared from lemon peel predominantly contains eriocitrin as an antioxidant. It is indicated to have low bioavailability compared with lemon flavonoid aglycone (LFA), which predomi- nantly contains eriodictyol. This study attempted to prepare LFA which has high bioavailability, using enzymes that are commonly used in the citrus industry, such as cellulase, naringinase, hesperidinase, and pectinase. LFA containing the highest amount of eriodictyol (19.4%) was prepared with naringinase, a debittering enzyme for citrus juice. Ten male normolipidemic subjects ingested LFA (3.7 g) after an over- night fast, and low-density lipoprotein (LDL) was prepared from 0-4 h plasma after intake of LFA. The LDL oxidizability was measured with lag time of the conjugated diene formation induced by an oxidative inducer. LDL in 0.5 h plasma after ingestion of LFA was shown to have a significantly longer lag time for oxidation than that before ingestion (P<0.05). LFA was suggested to have the resistance effect of LDL to oxidation ex vivo. Eriodictyol, homoeriodictyol, and hesperetin were not detected in plasma by HPLC analysis, but they were detected in plasma treated with β-glucuronidase and sulfatase.
    [Show full text]
  • C&T ® Key Points
    Research | C&T ® KEY POINTS • Oxidative stress caused by UV radiation and pollution causes damage to the hair follicle and contributes to premature hair loss. • In response, a yerba santa extract was assessed for its capability to protect hair follicles from oxidative damage and to reduce premature hair loss. facebook.com/CandTmagazine Cosmetics & Toiletries @cosmeticsandtoiletries Reproduction in English or any other language of 22 | www.CosmeticsandToiletries.comReproduction in English or any other languageall or partof all of or this part article of this is articlestrictly isprohibited. strictly prohibited. © 2020 Allured BusinessVol. Media.135, No. 6 | June 2020 © 2020 Allured Business Media. Hair Loss, UprootedFollicle Protection with Yerba Santa Christina Pickel, Ph.D., Franziska Wandrey, Ph.D., Daniel Schmid, Ph.D., and Fred Zülli, Ph.D. Mibelle Biochemistry, Buchs, Switzerland Marta Bertolini, Ph.D. Monasterium Laboratory, Münster, Germany ith the body, skin and scalp being the outermost boundaries of the body, they are exposed to a myriad of external stresses and pollution every day. Extensive studies over the years have shown that pollution and UV radiation can lead to premature skin aging, as they are W 1 some of the primary causes of reactive oxygen species (ROS). These highly reactive molecules cause damage to DNA, such as the formation of 8-hydroxydeoxyguanosin (8-OHdG) or the oxidation of fatty acids or amino acids in proteins, thereby potentially causing DNA mutations and impairing cell mem- brane or enzyme function. Detoxification of ROS is mediated by several cellular enzymes including catalase, superoxide dismutase or glu- tathione peroxidase.2 A key transcription factor involved in Cosmetics & Toiletries® | 23 Hair Loss, Uprooted Plants rich in polyphenolic compounds such as flavonoids have been shown to possess antioxidant activities.
    [Show full text]
  • UNITED STATES PATENT OFFICE 2,681,907 ISOATION of FILAWONOD COMPOUNDS Simon H
    Patented June 22, 1954 2,681,907 UNITED STATES PATENT OFFICE 2,681,907 ISOATION OF FILAWONOD COMPOUNDS Simon H. Wender, Norman, Okla., assignor to the United States of America as represented by the United States Atomic Energy Commission No Drawing. Application April 22, 1952, Serial No. 283,749 10 Claims. (C. 260-210) 1. 2 My invention relates to a method of purifying vide an improved method for isolating flavonoid flavonoids and more particularly to the recovery compounds. of quantities of substantially pure flavonoids Another object is to provide a method for iso from their naturally occurring source materials. lating relatively large quantities of a flavonoid The flavonoid compounds comprise a very in compound in Substantially pure form. portant class of plant pigments which are widely Still another object is to provide an improved distributed in the vegetable kingdom. Interest proceSS for Separating relatively pure flavonoids is shown in a number of these compounds due to in concentrated form from the original solid their vitamin-like action in increasing the resist source materials. ance of blood capillaries to rupture. The term O Further objects and advantages of my inven “vitamin P' is sometimes applied to flavonoids tion will be apparent from the following descrip having this property. Rutin, a member of this tion. class of plant pigments enjoys widespread use as In accordance with my invention, substantially a drug for blood vessel treatment. In addition, pure flavonoids may be separated in relatively it is anticipated that flavonoids will be of use in concentrated form from extraneous organic and the control of radiation injury, and considerable inoi'ganic impurities by preparing a water ex experimental effort is being expended in this tract of same, contacting said Water extract with direction.
    [Show full text]
  • CHAPTER 1 Introduction
    CHAPTER 1 Introduction Osteoporosis is the most common age-related conditions which is characterised by bone mineral density and change in microarchitecture of bone with consequently increasing in bone fragile(1). Osteoporosis has been reported to affect around 10% of population in North America, Europe and Japan(2). Considering the incidence rate of osteoporosis is anticipated to grow with increasing life expectancy. There is an extremely high mortality and morbidity due to bone fracture and loss ability to perform daily life activities. As a report from the World Health Organization (WHO) indicated the mortality and morbidity in Caucasian is as high as approximately 20% in 1-year post fracture. About 30% of survivors will have permanent disability with necessity of intensive care from others(3). For osteoporosis assessment, WHO first announced the tools for screening the patient with osteoporotic condition based on spinal mineral density (BMD) value. A person with osteoporosis has a BMD measurement of 2.5 standard deviations (SD) or more below of a young, normal adult of the same gender, according to WHO criterion(4). The International Osteoporosis Foundation (IOF) reported the project number of global osteoporotic fractures. As life expectancy continues to rise in many countries, approximately 323 million people aged 65 years or older in 1990 is predicted to surpass 1500 million by the year 2050. Together with the estimated number of hip fractures in 1990 may increase from 1.7 million to 6.3 million by the year 2050. Particularly in Asian population, the estimated number of hip fractures as 0.572 million in 1990 was expected to surpass 3.52 million by the year 2050(5).
    [Show full text]