DOCSLIB.ORG

A Food Toxicological Contemplation of Mycotoxins

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
A Food Toxicological Contemplation of Mycotoxins Author's copy! Any use beyond the limits of copyright law without the consent of the publisher is prohibited and punishable. This applies in particular to duplications, translations, microfilming as well as storage and processing in electronic systems. Science & Research | Overview Peer-reviewed | Manuscript received: January 31, 2013 | Revision accepted: May 08, 2013 A food toxicological contemplation of mycotoxins Pablo Steinberg, Hannover Metabolism Summary In order to become toxic, aflatoxin B1 Mycotoxins are the products of the endogenous metabolism of moulds that can must be metabolically activated v infest crops and already lead to adverse health effects in mammals and humans at ( Figure 3). Aflatoxin B1 is first me- low concentrations after the consumption of contaminated feed and food, re- tabolized to the aflatoxin B1-8,9- spectively. In the following report, the main mycotoxins detected in temperate epoxide in a cytochrome P450-cat- zones, namely aflatoxins, ochratoxin A, Fusarium mycotoxins (zearalenone, tri- alyzed reaction. Thereafter, the epox- 7 chothecenes and fumonisine), ergot alkaloids, patulin and citrinin, are briefly in- ide reacts with the N -position of troduced. In this context, their underlying mechanisms of toxicity, their main toxic guanine residues of the DNA and effects in humans and animals as well as the actual burden of foods with aflato- leads to the formation of the afla- 7 xins, ochratoxin A and Fusarium mycotoxins in Germany are described. toxin B1-N -guanine adduct. This adduct is chemically unstable and Keywords: Moulds, mycotoxins, aflatoxins, ochratoxin A, Fusarium toxins can be converted to the so-called aflatoxin B1-formamidopyrimidine adduct by the opening of the imida- zole ring or can decompose by taminate food items of plant and Introduction depurination and lead to an apurinic animal origin (v Figure 1). site in DNA. Products of the endogenous metabo- lism of moulds which can be harm- In this contribution, information re- In both cases, DNA replication leads ful to humans and other living or- garding the most relevant mycotox- to gene mutations, whereby afla- ganisms, are grouped under the ge- ins from a food toxicological point of toxin B1 is a much stronger mutagen neric term „mycotoxins“. Myco- view, namely aflatoxins, ochratoxin than aflatoxin G1 and aflatoxin M1. toxins can be formed by outdoor A, Fusarium mycotoxins, ergot alka- In contrast, the aflatoxins B2, G2 und moulds (e. g. Fusarium spp.), which loids, patulin und citrinin, is sum- M2, which cannot be epoxidized, are can infest the crops already in the marized. hardly genotoxic. Aflatoxin B1 also field, as well as by indoor moulds exhibits a pronounced cytotoxicity (e. g. Aspergillus spp., Penicillium Aflatoxins which is in part due to the signifi- spp.), which can infest the harvested cant formation of covalent protein crops if they are stored inappropria- Aflatoxins are products of the en- adducts. In this case again it is the tely (i. e. too high storage humidity, dogenous metabolism of the moulds aflatoxin B1-8,9-epoxide that plays a too long intervals between the har- Aspergillus flavus, Aspergillus para- central role: It is first metabolized to vesting and the drying step or insuf- siticus and Aspergillus oryzae, which the corresponding dihydrodiol and ficient airing). Once they have been pose a great problem in tropical and then to the corresponding dialdehyde released by moulds, they may con- subtropical regions of the world. (v Figure 3). The dialdehyde in turn Consequently, aflatoxins are mainly can easily react with the ε-amino detected in imported products such groups of lysine. as nuts (pistachios, peanuts, hazel- Citation: nuts), dried fruit (figs) and spices Toxicity Steinberg P (2013) A food toxico- (pepper, paprika powder). Aflatoxin logical contemplation of myco- B1, aflatoxin B2, aflatoxin G1 and In countries, in which the contami- toxins. Ernaehrungs Umschau in- aflatoxin G2 as well as aflatoxin M1 nation of the food chain with afla- v ternational 60(9): 146–151 and aflatoxin M2 ( Figure 2), which toxins is very high, so-called aflato- This article is available online: are mainly detected in milk and milk xicoses may develop. They are cha- DOI 10.4455/eu.2013.027 products, belong to the group of the racterized by nausea, vomiting, ab- aflatoxins. dominal pain and gastrointestinal 146 Ernaehrungs Umschau international | 9/2013 bleeding, icterus, spasms, coma, Ochratoxin A O O O O pulmonary and cerebral oedema O O Ochratoxins are produced by vari- 9 R R formation as well as necroses and 8 ous Aspergillus and Penicillium fatty degeneration of the liver, kid- O O O O neys and heart. species, among others by Aspergillus H OCH3 H OCH3 ochra ceus, Aspergillus carbonarius AFB1: R = H AFB2: R = H AFM : R = OH AFM : R = OH and Penicillium verrucosum, and 1 2 Because of its extremely strong mu- O O O O tagenicity and cytotoxicity (see chemically represent amide deriva- O O tives of L-phenylalanine (v Figure R R above) aflatoxin B1 is the aflatoxin 4). with the greatest carcinogenic po- O O O OCH O OCH tential and induces liver tumours in The most frequently formed and at H 3 H 3 AFG1: R = H AFG2: R = H experimental animals. The Interna- the same time the most toxic ochra- AFGM1: R = OH AFGM2: R = OH tional Agency for Research on Can- toxin is ochratoxin A. It contami- cer (Lyon, France) which is part of nates grains and grain products, Fig. 2: Structural formulae of the most impor- the World Health Organization legumes, coffee beans, beer, wine, tant aflatoxins in food (WHO), classified aflatoxin B1 as a raisins, grape juice as well as meat AFB1/2 = aflatoxin B1/2, AFM1/2 = aflatoxin human carcinogen a decade ago [1]. products and is mainly nephrotoxic. M1/2, AFG1/2 = aflatoxin G1/2, AFGM1/2 = aflatoxin GM The chronic exposure of humans to It has been known for a long time 1/2 aflatoxin B1 also leads to the induc- that because of its structural ho- AFB -N7-G mology to the amino acid L-pheny- 1 tion of liver carcinomas. Moreover, H N - dR 2 H2N NH NH lalanine ochratoxin A is able to in- O it has been known for a number of N O O N O O O OH H2O OH O + O years that the risk to develop liver hibit competitively the phenylala- N HN H N 7 H dR dR N O O tumours increases by about a factor nine-tRNA-synthase. However, the H O O H OCH3 H O OCH above-mentioned enzyme is only 3 of 60 if humans are chronically ex- AFB 1 -FAPY DNA O O posed to aflatoxins through con- inhibited in the presence of very O O O O O 9 H H taminated food and at the same time high concentrations of ochratoxin 8 CYP O O are chronically infected with hepati- A, which in no case are achieved if H O OCH O 3 H OCH3 tis B or C viruses. It has also been humans are exposed to ochratoxin AFB1 AFB1-8,9-epoxide GSH O O A-contamined food items. Hence, H2O pointed out that a relationship be- OH O O GS H O tween the strong contamination of the inhibition of the phenylalanine- OH O O HO H H O the food chain with aflatoxins and tRNA-synthase does not explain the OCH3 O GSH adduct H O OCH the occurrence of the so-called Reye observed renal toxicity. 3 – CO2 AFB1-8,9-diol + syndrome (an acute encephalopathy HC NH3 O O O in combination with a fatty degen- Ochratoxin A induces kidney tu- (H C) O H O 2 3 O Lysin OH O O eration of the liver), most notably in mours in rats. However, the mech- H2C N H HO OCH3 O tropical countries, may exist. anism(s) that lead(s) to the forma- HO OCH3 lysine adduct Fig. 3: Metabolic activation of aflatoxin B1 to aflatoxin B1-8,9-epoxide and forma- primary production feed storage tion of covalent adducts with DNA und proteins AFB1 = aflatoxin B1; AFB1-FAPY = aflato- xin B1-formamidopyrimidine adduct; outdoor moulds indoor moulds 7 7 AFB1-N -G = aflatoxin B1-N -guanine ad- duct; CYP = cytochrome P450; dR = de- oxyribose; GSH = glutathione contamination of feed contamination of food of plant O OR1 origin O O O exposure of livestock N O H CH3 R2 OTA: R1 = H; R2 = CI contamination of food of animal OTB: R1 = H; R2 = H origin 1 2 OTC: R = C2H5; R = CI Fig. 4: Structural formulae of the most im- Fig. 1: Contamination of food items of plant and animal origin with portant ochratoxins toxins from outdoor and indoor moulds OTA/B/C = ochratoxin A/B/C Ī Ernaehrungs Umschau international | 9/2013 147 Science & Research | Overview tion of kidney tumours have been other hand, no efficient crop clean- to estrogen receptors in the uterus, controversially discussed up to the up took place in the flour mills. hypothalamus and pituitary gland. present time. Although there were Despite efforts to reduce the amount The affinity of zearalenone to the es- early indications that DNA adducts of ocharoxin A in food items, a cer- trogen receptors α and β is about one are formed in the kidneys of ochra- tain degree of contamination seems tenth to one twentieth of the affinity toxin A-treated rats, it is not clear to be unavoidable at the moment. of the endogenous estrogen 17β- whether these are oxidative DNA le- The tolerable weekly intake amounts estradiol towards the estrogen recep- sions or covalent adducts of DNA to 120 ng/kg body weight. In the tors α and β.
Load more

Recommended publications
  • Nematotoxicity of Neotyphodium Infected Tall Fescue Alkaloids and Other Secondary Metabolites on Pratylenchus Scribneri
    NEMATOTOXICITY OF NEOTYPHODIUM-INFECTED TALL FESCUE ALKALOIDS AND OTHER SECONDARY METABOLITES ON THE PLANT- PARASITIC NEMATODE PRATYLENCHUS SCRIBNERI by ADA ANTONIA BACETTY (Under the direction of Charles W. Bacon) ABSTRACT Tall fescue (Festuca arundinacea) is a perennial, cool-season turf and forage grass species in the United States that covers over 20 million hectares of pastureland. Neotyphodium coenophialum, an endophytic fungus associated with cool-season grasses, enhances host fitness and imparts pest resistance to the grass. Biologically active alkaloids and other secondary metabolites are produced in this association that not only cause adverse effects on livestock, fescue toxicosis, but may also play a role in the reduction of plant-parasitic nematode populations. Currently there is little information available on the effects of these biologically active compounds on nematodes associated with tall fescue. Therefore, this research examines the interaction of ergot and loline alkaloids, as well as polyphenolic compounds, from endophyte-infected tall fescue on toxicity to the lesion nematode, Pratylenchus scribneri. In vitro bioassays were performed to assess the effects of specifically identified compounds on P. scribneri motility, mortality, and chemoreception. While separate greenhouse studies evaluated the effects of endophyte- infected tall fescue on P. scribneri viability. Root extracts served as nematistatic agents to the nematodes in the chemical submersion assays and affected nematode behavior by acting as repellents in chemoreception studies. During individual tests, ergovaline and α-ergocryptine were nematicidal at 5µg/ml and 50µg/ml respectively. However, chemotaxis studies revealed α-ergocryptine as an attractant (1-20µg/ml) and repellent (50-200µg/ml). Ergovaline was an effective repellent (1-5µg/ml) and a nematicidal (10-200µg/ml).
    [Show full text]
  • Occurrence and Significance of Mycotoxins in Forage Crops And
    J Sci Food Agric 1998, 77,1È17 Occurrence and Signiücance of Mycotoxins in Forage Crops and Silage: a Review Keith A Scudamore1* and Christopher T Livesey2 1 Central Science Laboratory, London Road, Slough, Berks, SL3 7HJ, UK 2 Veterinary Laboratories Agency, New Haw, Woodham Lane, Addlestone, Surrey, KT15 3NB, UK (Received 5 December 1996; revised version received 29 May 1997; accepted 4 September 1997) Abstract: Study of mycotoxins in animal feeding stu†s has concentrated on the occurrence of aÑatoxins and, to a lesser extent, other mycotoxins in cereals, raw materials and concentrate feeds. However, ruminant diets contain a high propor- tion of forage crops such as grass or maize silage, hay and straw. Under adverse growing, production or storage conditions, fungal spoilage is likely to occur with some degree of mycotoxin contamination. The mould Ñora of forage crops is likely to di†er signiÐcantly from that of cereals and mycotoxin contamination, should it occur, could di†er qualitatively and quantitatively. Information relating to forage crops as a potential source of mycotoxins is reviewed. Some Ðeld inci- dents and animal disease which may be mycotoxin related are discussed and analytical methods are reviewed. Information on dose and e†ect of candidate mycotoxins is given where available. The review suggests areas which the authors consider merit further study. Crown Copyright 1998. J Sci Food Agric 77,1È17 (1998) Key words: mycotoxins; fungi; moulds; silage; forage crops; hay; straw; occurrence; analysis; risk assessment; animal disease INTRODUCTION access, silage will be at risk from storage moulds such as Penicillium and Aspergillus. However, moulds may be During growth, forage crops are at risk in the Ðeld from aerobic or anaerobic and this means that, even if infection by a number of di†erent fungi, some of which oxygen is excluded, some moulds may be able to may produce mycotoxins.
    [Show full text]
  • Cover Next Page > Cover Next Page >
    cover next page > Cover title: The Psychopharmacology of Herbal Medicine : Plant Drugs That Alter Mind, Brain, and Behavior author: Spinella, Marcello. publisher: MIT Press isbn10 | asin: 0262692651 print isbn13: 9780262692656 ebook isbn13: 9780585386645 language: English subject Psychotropic drugs, Herbs--Therapeutic use, Psychopharmacology, Medicinal plants--Psychological aspects. publication date: 2001 lcc: RC483.S65 2001eb ddc: 615/.788 subject: Psychotropic drugs, Herbs--Therapeutic use, Psychopharmacology, Medicinal plants--Psychological aspects. cover next page > < previous page page_i next page > Page i The Psychopharmacology of Herbal Medicine < previous page page_i next page > cover next page > Cover title: The Psychopharmacology of Herbal Medicine : Plant Drugs That Alter Mind, Brain, and Behavior author: Spinella, Marcello. publisher: MIT Press isbn10 | asin: 0262692651 print isbn13: 9780262692656 ebook isbn13: 9780585386645 language: English subject Psychotropic drugs, Herbs--Therapeutic use, Psychopharmacology, Medicinal plants--Psychological aspects. publication date: 2001 lcc: RC483.S65 2001eb ddc: 615/.788 subject: Psychotropic drugs, Herbs--Therapeutic use, Psychopharmacology, Medicinal plants--Psychological aspects. cover next page > < previous page page_ii next page > Page ii This page intentionally left blank. < previous page page_ii next page > < previous page page_iii next page > Page iii The Psychopharmacology of Herbal Medicine Plant Drugs That Alter Mind, Brain, and Behavior Marcello Spinella < previous page page_iii next page > < previous page page_iv next page > Page iv © 2001 Massachusetts Institute of Technology All rights reserved. No part of this book may be reproduced in any form by any electronic or mechanical means (including photocopying, recording, or information storage and retrieval) without permission in writing from the publisher. This book was set in Adobe Sabon in QuarkXPress by Asco Typesetters, Hong Kong and was printed and bound in the United States of America.
    [Show full text]
  • Introduction to the Pharmacology of Ergot Alkaloids and Related Compounds As a Basis of Their Therapeutic Application
    CHAPTER I Introduction to the Pharmacology of Ergot Alkaloids and Related Compounds as a Basis of Their Therapeutic Application B. BERDE and E. STURMER "Truth is rarely pure and never simple" OSCAR WILDE This chapter, rather unorthodox for a volume of the Handbook of Experimental Pharmacology, is not intended as a summary of the wealth of information accumu- lated in this book. It is an attempt at a compact synopsis to help those teaching pharmacology or writing a textbook of pharmacology not to overlook the essential chemical and biological basis of the therapeutically most important compounds and those of their activities which are believed to be relevant for their therapeutic effects. The present volume, entitled Ergot Alkaloids and Related Compounds, deals with chemical entities containing the tetracyclic ergolene- or ergoline-ring system. They can be obtained by extraction of different strains of the fungus cIaviceps- grown on rye or cultivated in fermentation tanks-or alternatively by partial or total synthesis. These compounds can be divided into four main structural groups: cIavine alkaloids, lysergic acids, simple lysergic acid-amides, and peptide alkaloids. One example of each type of molecule is given in Figure 1. The degree of oxidation is a criterion for further differentiation in the group of cIavine alkaloids, all of which are compounds of minor biological importance. The naturally occurring lysergic acids are divided into compounds with a double bond in the 8-9 position (8-ergolenes) and in the 9-10 position (9-ergolenes). All congeners are methylated in position (i. The two asymmetric carbon atoms in position 5 and 10 (in the case of 8-ergolenes) or 5 and 8 (in the case of Glavine-Alkaloids Lysergic Acid group Lysergic Acid Amides Peptide-Alkaloids of Alkaloids Examples: I'_ GOOH I"'" NH'GH3 b ~HN Elymoclavine D-Lysergic Acid Ergometrine Ergotamine Fig.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2004/0132780 A1 Allen Et Al
    US 2004O132780A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2004/0132780 A1 Allen et al. (43) Pub. Date: Jul. 8, 2004 (54) METHOD AND COMPOSITIONS FOR (52) U.S. Cl. .............................................................. 514/334 TREATING MIGRAINES (76) Inventors: Christopher P. Allen, Doylestown, PA (57) ABSTRACT (US); Phyllis W. Stone, Somerset, NJ (US); Sean Harper, Gwynedd Valley, The present invention relates to a method for treating or PA (US) preventing migraines in a mammalian patient in need of Such treatment or prevention comprising administering to Correspondence Address: Said patient a compound of Formula A or a pharmaceutically MERCKAND COINC Salt, hydrate or N-oxide thereof, in an amount that is PO BOX 2000 effective to treat or prevent migraines. RAHWAY, NJ 070650907 (21) Appl. No.: 10/476,753 (A) SOCH (22) PCT Filed: Apr. 30, 2002 (86) PCT No.: PCT/US02/13750 C N (30) Foreign Application Priority Data 4. N May 4, 2001 (US).......................................... 60/288623 2 Publication Classification (51) Int. Cl." ............................................ A61K 31/444 US 2004/O132780 A1 Jul. 8, 2004 METHOD AND COMPOSITIONS FOR TREATING DETAILED DESCRIPTION MIGRAINES 0007. The present invention encompasses a method for BACKGROUND OF THE INVENTION treating or preventing migraines in a mammalian patient in need of Such treatment or prevention comprising adminis 0001 Migraines are recurrent, often familial, symptom tering to Said patient a compound of Formula A: complexes of periodic attacks of vascular headache. The condition is characterized by intermittent attacks of head ache, preceded by an aura in approximately 15% of patients. The headache is often accompanied by associated Symp SOCH3 toms, most commonly nausea, vomiting, photophobia and phonophobia.
    [Show full text]
  • Studies of Ergot Alkaloid Biosynthesis Genes in Clavicipitaceous Fungi
    University of Kentucky UKnowledge University of Kentucky Doctoral Dissertations Graduate School 2004 STUDIES OF ERGOT ALKALOID BIOSYNTHESIS GENES IN CLAVICIPITACEOUS FUNGI Caroline Machado University of Kentucky, [email protected] Right click to open a feedback form in a new tab to let us know how this document benefits ou.y Recommended Citation Machado, Caroline, "STUDIES OF ERGOT ALKALOID BIOSYNTHESIS GENES IN CLAVICIPITACEOUS FUNGI" (2004). University of Kentucky Doctoral Dissertations. 433. https://uknowledge.uky.edu/gradschool_diss/433 This Dissertation is brought to you for free and open access by the Graduate School at UKnowledge. It has been accepted for inclusion in University of Kentucky Doctoral Dissertations by an authorized administrator of UKnowledge. For more information, please contact [email protected]. ABSTRACT OF DISSERTATION Caroline Machado The Graduate School University of Kentucky 2004 STUDIES OF ERGOT ALKALOID BIOSYNTHESIS GENES IN CLAVICIPITACEOUS FUNGI ABSTRACT OF DISSERTATION A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the College of Agriculture at the University of Kentucky By Caroline Machado Lexington, Kentucky Director: Dr. Christopher L. Schardl, Professor of Plant Pathology Lexington, Kentucky 2004 Copyright by Caroline Machado 2004 ABSTRACT OF DISSERTATION STUDIES OF ERGOT ALKALOID BIOSYNTHESIS GENES IN CLAVICIPITACEOUS FUNGI Neotyphodium species, endophytic fungi associated with cool-season grasses, enhance host fitness and stress tolerance, but also produce biologically active alkaloids including ergot alkaloids associated with fescue toxicosis in grazing animals. One approach to reduce fescue toxicosis is to manipulate genes in the ergot alkaloid pathway. The gene, dmaW, encoding the first pathway-specific step in ergot alkaloid biosynthesis, was cloned previously from Claviceps spp.
    [Show full text]
  • Nomination Background: Hydergine (CASRN: 8067-24-1)
    SUMMARY OF DATA FOR CHEMICAL SELECTION Hydergine®1 8067-24-1 BASIS OF NOMINATION TO THE CSWG Hydergine was identified from a review of substances being promoted as nootropics or "smart drugs" for cognition enhancement in well persons of all ages. Hydergine is also a prescription drug for the treatment of senility and cerebrovascular insufficiency. Hydergine is an ergot alkaloid. Ergot alkaloids have a wide field of therapeutic application, and their biological activities are strongly dependent on their structural conformation. Despite their widespread use, little information on the carcinogenic or mutagenic potential of hydergine or closely related ergot alkaloids was found in the available literature. Information on the genotoxicity of hydergine was mixed and not completely consistent with the results reported for the closely related compound, ergotamine. SELECTION STATUS ACTION BY CSWG: 12/16/99 Studies requested: Standard battery of genotoxicity tests including Ames Salmonella and micronucleus assays Priority: The CSWG does not assign priority to genotoxicity testing Rationale/Remarks: An ergot alkaloid prescription drug recently promoted for use as a “smart drug” for healthy individuals seeking cognition enhancement Mixed results regarding genotoxicity; no information on carcinogenicity Ergot alkaloids have a wide range of effects influenced by small changes in structure which affect receptor site binding 1Hydergine® is a registered trademark of Sandoz Pharmaceuticals; the drug will be referred to as "hydergine" for the purpose of
    [Show full text]
  • United States Patent Office Patented Jan
    3,557,287 United States Patent Office Patented Jan. 19, 1971 2 3,557,287 teral administration, e.g. tablets, dragées, capsules, Sup COMPOSITIONS AND METHODS FOR TREATING positories and injectable solutions. In order to produce HEADACHES OF WASCULAR ORIGIN WITH Such medicinal preparations the mixture of active con COMBINATIONS OF CAFFEINE, A VASOTONIC stituents is worked up with the usual organic or inorganic, LYSERGEC ACED AND A THOXANTHENE pharmacologically inert adjuvants. Examples of such ad Botond Berde and Albert Fanchamps, Basel, Switzerland, assignors to Sandoz Ltd. (also known as Sandoz AG), juvants are lactose, starch, polyvinyl pyrrollidone, stearic Basel, Switzerland acid, sorbic acid, talc, methyl cellulose, alcohols, glycerin No Drawing. Filed Dec. 31, 1968, Ser. No. 788,351 and natural or hardened oils. The preparations may fur Claims priority, application Switzerland, Jan. 9, 1968, thermore contain suitable sweetening or colouring sub 350/68 10 stances and flavourings. Int, C. A61k 27/00 U.S. Cl, 424-253 6 Claims EXAMPLES OF GALENIC PREPARATIONS Example 1.--Capsules (composition A) ABSTRACT OF THE DISCLOSURE G. 5 Ergostine hydrogen maleate ---------------- 10.0012 The invention relates to a pharmaceutical composition Caffeine (anhydrous) --------------------- 0.10 incorporating as active constituents: Mepithiathene hydrogen maleate ------------ 20.0007 (a) a vasotonic lysergic acid derivative of the peptide Tale ------------------------------------ 0.050 type or a pharmaceutically acceptable acid addition 20 Lactose --------------------------------- 0.1381. salt thereof; (b) caffeine; and Content of the capsule --------------- 0.290 (c) 9-(1-methyl - 4 - piperidylidene)thioxanthene or a Cover about ----------------------- 0.080 pharmaceutically acceptable acid addition salt thereof. For a capsule of about --------------- 0.370 The composition is useful for treating attacks of mi Corresponds to 0.0010 g.
    [Show full text]
  • Targeted and Untargeted Analysis of Secondary Fungal Metabolites by Liquid Chromatography-Mass Spectrometry
    Targeted and untargeted analysis of secondary fungal metabolites by liquid chromatography-mass spectrometry Svetlana V. Malysheva Promoter: Prof. Dr. Sarah De Saeger Co-promoters: Prof. Dr. Irina Yu. Goryacheva Dr. José Diana Di Mavungu 2013 THESIS SUBMITTED IN FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR IN PHARMACEUTICAL SCIENCES PROEFSCHRIFT VOORGELEGD TOT HET BEKOMEN VAN DE GRAAD VAN DOCTOR IN DE FARMACEUTISCHE WETENSCHAPPEN Targeted and untargeted analysis of secondary fungal metabolites by liquid chromatography-mass spectrometry Svetlana V. Malysheva Promoter: Prof. Dr. Sarah De Saeger Co-promoters: Prof. Dr. Irina Yu. Goryacheva Dr. José Diana Di Mavungu 2013 THESIS SUBMITTED IN FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR IN PHARMACEUTICAL SCIENCES PROEFSCHRIFT VOORGELEGD TOT HET BEKOMEN VAN DE GRAAD VAN DOCTOR IN DE FARMACEUTISCHE WETENSCHAPPEN PhD thesis Title: Targeted and untargeted analysis of secondary fungal metabolites by liquid chromatography – mass spectrometry Author: Svetlana V. Malysheva Year: 2013 Pages: 338 ISBN: 978-94-6197-128-9 Printer: University Press, Zelzate, Belgium Refer to this thesis as follows: Malysheva SV (2013). Targeted and untargeted analysis of secondary fungal metabolites by liquid chromatography – mass spectrometry. Thesis submitted in fulfilment of the requirements of the degree of Doctor (Ph.D.) in Pharmaceutical Sciences. Faculty of Pharmaceutical Sciences, Ghent University Promoter: Prof. Sarah De Saeger (Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium) Co-promoters: Prof. Irina Yu. Goryacheva (Chemistry Institute, Saratov State University, Russia) Dr. José Diana Di Mavungu (Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium) Members of the reading committee: Prof. Ann Van Schepdael (Faculty of Pharmaceutical Sciences, KU Leuven, Belgium) Prof.
    [Show full text]
  • I ASPECTS of ERGOT ALKALOID BIOSYNTHESIS a Thesis Presented
    I ASPECTS OF ERGOT ALKALOID BIOSYNTHESIS A thesis presented by FRANCOISE QUIGLEY In part fulfilment of the requirements for the degree of Doctor of Philosophy, of the University of London Imperial College November 1973 Biochemistry Department ABSTRACT Methods of isolation and purification of ergot alkaloids were investigated with reference to the following chromatographic techniques: thin layer chromatography (T.L.C.), gas liquid chromatography (G.L.C.) and the use of neutral and ion-exchange chromatography. Sephadex SP C-25 ion-exchange resin, in appropriate ionic form, selectively absorbed ergot alkaloids from culture extracts and gave not only a separation of the basic and amphoteric fractions but also separated the peptide and clavine ergot alkaloids. G.L.C. analysis of Claviceps fusiformis extracts was achieved by trifluoroacetylation and silylation. The three major ergot alkaloids present in the amphoteric fraction of Claviceps fusiformis extracts were identified as 4-dimethylallyl- tryptophan, clavicipitic acid, and N-methyl-4-dimethylallyltryptophan. The latter, a new isolate, was observed to accumulate under anaerobic conditions. The inter-relationship of the clavine alkaloids was investigated in 14 Claviceps fusiformis by a kinetic feeding experiment using (2- C) tryptophan as the precursor. Results agreed with the generally accepted scheme of ergot alkaloid biosynthesis in Claviceps spp. tryptophan dimethylallyl- mevalonic ---4 tryptophan ___4 chanoclavine-I ---> agroclavine acid elymoclavine The presence of other biosynthetic intermediates, hydroxylated clavines, _ 14 was also suggested. Feeding of (3'-2H3, 2- C) mevalonate confirmed the general scheme above and provided further evidence for the loss from ) C-3 of mevalonate,of 1 and 2 protons in the enzymatic formation of chanoclavine I and agroclavine respectively.
    [Show full text]
  • Btochelylirftl INTERACTIONS INVOLVING PARASITTE Clavicepx Purpurea
    1. BTOCHElYlirftl INTERACTIONS INVOLVING PARASITTE Clavicepx purpurea A thesis presented in fulfilment of the requirements for the degree of Ph.D. of the University of London by JULIA WILLINGALE April 1983 Department of Biochemistry, Imperial College of Science and Technology, London, SU7. 2. BIOCHEMICAL INTERACTIONS INVOLVING PARASTIC CJavicens PURPUREA ABSTRACT Artificial inoculation of wheat, infected with the bunt fungus Tilletia caries with Claviceps purpurea strain 12/2 [ALK~] resulted in a dual infection of the host ovary. Spatial interaction between the two pathogens during concurrent occupation of the ovary were studied by immunofluorescent microscopy, based on antibody raised against C. purpurea glucanase. Experiments on the specificity of this antibody showed no cross reaction with the mycelium of T. caries grown in axenic culture. Using this apparent specificity the investigations revealed penetration through the integument wall at the base of the ovary. Within 5 days, T. caries teliospores, at the base of the ovary, had been displaced in an acropetal direction by sporing,sphacelial tissue of C, purpurea. Establishment of the sphacelium was marked by copious honeydew exudation. At the fungal-fungal interface teliospores were completely surrounded by Claviceps hyphae. Above and below this interface, free teliospores and homogeneous sphacelial tissue were evident. As growth and differentiation to sclerotial tissue occurred, the bunted region became pushed to the tip of the developing ergot, forming a cap of black teliospores. During parasitic development on rye, a strain of Claviceps purpurea produced the primary pathway precursor dimethylaliyltryptophan (DMAT) but no tetracyclic ergoline alkaloids. Incubation of fresh sclerotial tissue with radioactively labelled primary pathway precursors demonstrated the biosynthesis of DMAT during the incubation period from tryptophan and mevalonate.
    [Show full text]
  • ASPECTS of the PRODUCTION of ALKALOIDS in PENICILLIUM and CLAVICEPS. a Thesis Submitted in Fulfilment of the Requirements Of
    ASPECTS OF THE PRODUCTION OF ALKALOIDS IN PENICILLIUM AND CLAVICEPS. A thesis submitted in fulfilment of the requirements of the University of London for the award, Ph.D. JULY 1990 Jane Marina Boyes-Korkis Department of Biochemistry Imperial College of Science, Technology and Medicine, London. SW7. ABSTRACT. [*4C-carbonyl]-anthranilic acid has been used as a biosynthetic probe in a search for novel benzodiazepines. A novel benzodiazepine comprising anthranilic acid and leucine, which together form the benzodiazepine nucleus, and which is substituted by a cyclic glutarimide function has been isolated from liquid cultures of Penicillium aurantiogriseum. In addition a novel diketopiperazine comprising tryptophan and phenylalanine has been isolated. The novel diketopiperazine contains an inverted isoprene group and also exhibits rather rare N-acetylation of the indolic moiety. The structures of the novel compounds were determined by a combination of spectroscopic techniques, particularly JH- and 13C-NMR spectroscopy. Confirmation of the participation of anthranilic acid, leucine and glutamate in the biosynthesis of the benzodiazepine and of the involvement of tryptophan in the formation of the diketopiperazine has been achieved by radiolabelled precursor feeding experiments. Process development of large-scale fermentation of P. aurantiogriseum was necessary to obtain a sufficient amount of each metabolite for structural determination and so the dynamics of the fermentation were also followed. As a prelude to isolation of the enzyme catalysing an isoprenyl- ation step in secondary biosynthesis of P. aurantiogriseum a model system, appertaining to the first enzyme in alkaloid biosynthesis in C laviceps, has been explored for experience, critical appraisal and development of the special techniques involved.
    [Show full text]