zendah el euch

322 Pages·2012·3.73 MB·English

ZENDAH EL EUCH
___________________________________________

Isolation, Purification and Structure Elucidation
of New Secondary Metabolites from Terrestrial,
Marine, and Ruminal Microorganisms

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Dissertation
Isolation, Purification and Structure Elucidation of New Secondary Metabolites
from Terrestrial, Marine and Ruminal Microorganisms

Dissertation
zur Erlangung des Doktorgrades
der Mathematisch-Naturwissenschaftlichen Fakultäten
der Georg-August-Universität zu Göttingen

vorgelegt von
Imène ZENDAH EL EUCH
aus
Tunesien

Göttingen 2012

D7
Referent: Prof. Dr. H. Laatsch
Referent: Prof. Aly Raies
Korreferent: Prof. Dr. A. Zeeck
Tag der mündlichen Prüfung: 13. Juli 2012
Die vorliegende Arbeit wurde in der Zeit von Oktober 2005 bis März 2007 in der
Faculté des Sciences de Tunis (Laboratoire des Microorganismes et des Bio-
molécules Actives) unter der Leitung von Herrn Prof. RAIES Aly und von April
2007 bis Juli 2012 im Institut für Organische und Biomolekulare Chemie der Georg-
August-Universität zu Göttingen unter der Leitung von Herrn Prof. Dr. H. Laatsch
angefertigt.
Herrn Prof. Dr. H. Laatsch danke ich für die Möglichkeit zur Durchführung dieser
Arbeit sowie die ständige Bereitschaft, auftretende Probleme zu diskutieren.
Für meine Eltern, meine Geschwister
und meinen Ehemann
Content I

TABLE OF CONTENTS
1 INTRODUCTION ...................................................................................................................... 1
1.1 NATURE AS A SOURCE OF NATURAL PRODUCTS .................................................................... 1
1.2 NATURAL PRODUCTS AS PHARMACEUTICAL DRUGS FROM TERRESTRIAL BACTERIA ......... 10
1.3 MARINE NATURAL PRODUCTS AS PHARMACEUTICAL DRUGS ........................................... 16
1.4 RUMINAL BACTERIA AS NEW SOURCES OF POTENTIAL ANTIMICROBIALS ........................... 23
2 AIM OF THE PRESENT WORK ........................................................................................... 25
3 GENERAL TECHNIQUES ..................................................................................................... 27
3.1 COLLECTION OF STRAINS ................................................................................................... 27
3.2 WORK UP PROCEDURE FOR SELECTED BACTERIAL STRAINS ............................................... 28
3.3 PRE-SCREENING ................................................................................................................. 28
3.3.1 Biological screening ............................................................................................ 29
3.3.2 Chemical screening ............................................................................................. 29
3.3.3 Pharmacological and biological assays .............................................................. 30
3.4 CULTIVATION AND SCALE-UP ............................................................................................. 31
3.5 ISOLATION METHODS ......................................................................................................... 31
3.6 PARTIAL IDENTIFICATION AND DEREPLICATION ................................................................. 32
4 INVESTIGATION OF SELECTED BACTERIAL AND FUNGAL STRAINS: RUMINAL
BACTERIA ......................................................................................................................................... 33
4.1 RUMINAL PSEUDOMONAS AERUGINOSA ZIO ....................................................................... 33
4.1.1 1H-Quinazoline-2,4-dione ................................................................................... 36
4.1.2 Barakacin ............................................................................................................. 38
4.1.3 Rhamnolipid A (Glycolipid A): ............................................................................ 49
4.1.4 Phenazine-1-carboxylic acid ............................................................................... 53
4.1.5 3-(Hydroxyacetyl)-indole ..................................................................................... 54
4.1.6 Indole-3-carbaldehyde ......................................................................................... 56
4.1.7 Cyclo(Phe,Pro) .................................................................................................... 56
4.1.8 Triethylamine ....................................................................................................... 58
4.2 RUMINAL BACTERIUM CITROBACTER FREUNDII ZIG ........................................................... 60
4.2.1 Oleic acid ............................................................................................................. 61
4.2.2 Isoxanthohumol.................................................................................................... 63
4.2.3 Cis-Cyclo(Pro,Leu) .............................................................................................. 65
4.2.4 Cyclo(Tyr,Pro) ..................................................................................................... 66
4.2.5 Phenol .................................................................................................................. 67
4.2.6 Adenine ................................................................................................................ 68
Content

4.3 RUMINAL BACTERIUM GEMELLA MORBILLORUM ZIK .......................................................... 70
4.3.1 Anthranilic acid ................................................................................................... 71
4.3.2 1-Hydroxy-4-methoxy-2-naphthoic acid .............................................................. 72
4.4 RUMINAL BACTERIUM ENTEROBACTER AMNIGENUS ZIH ..................................................... 74
4.4.1 N -Acetyltryptamine ............................................................................................. 75
ß
4.4.2 Tyrosol ................................................................................................................. 76
4.4.3 Phenol .................................................................................................................. 78
4.4.4 Tryptophol ........................................................................................................... 78
4.4.5 Brevinic acid ........................................................................................................ 79
4.4.6 Indole-3-lactic acid .............................................................................................. 81
4.4.7 Butyl glycoside ..................................................................................................... 82
4.4.8 Other metabolites ................................................................................................ 84
4.5 RUMINAL SERRATIA RUBIDAE ZIE ........................................................................................ 85
4.5.1 Surfactin derivative .............................................................................................. 87
4.5.2 Prodigiosin .......................................................................................................... 90
4.5.3 Indole-3-acetic acid ............................................................................................. 91
4.5.4 1-Acetyl-β-carboline ............................................................................................ 92
4.5.5 4-Hydroxy-5-methyl-furan-3-one ........................................................................ 93
4.5.6 Actinomycin D ..................................................................................................... 94
4.6 RUMINAL KLEBSIELLA PNEUMONIAE ZIC .......................................................................... 96
4.6.1 4',5,7-Trihydroxyisoflavone (genisteine) ............................................................. 98
4.6.2 4-Hydroxybenzoic acid ...................................................................................... 100
4.7 RUMINAL BACTERIUM PSEUDOMONAS AERUGINOSA ZIL ................................................... 100
4.7.1 2-n-Heptyl-1-hydroxy-1H-quinolin-4-one ......................................................... 102
4.7.2 3-n-Heptyl-3-hydroxy-1,2,3,4-tetrahydroquinoline-2,4-dione ........................... 107
4.7.3 Polypropylenglycol ............................................................................................ 109
4.7.4 1-Phenazinol ...................................................................................................... 110
4.7.5 Phenazine-1-carboxamide ................................................................................. 112
4.7.6 Rhamnolipid A and rhamnolipid B .................................................................... 113
5 TERRESTRIAL BACTERIA ................................................................................................ 115
5.1 TERRESTRIAL BACILLUS SP. ZIR ....................................................................................... 115
5.1.1 Monensin B ........................................................................................................ 116
5.2 TERRESTRIAL PSEUDOMONAS SP. ZIPS ............................................................................. 120
5.2.1 Linoleic acid ...................................................................................................... 121
5.3 TERRESTRIAL STREPTOMYCES SP. 195 ............................................................................... 122
5.3.1 5-Hydroxymethyl-3-(1-hydroxy-6-methyl-heptyl)-dihydrofuran-2-one ............. 123