Bioactive Natural Products: Chemistry and Biology

544 Pages·2015·5.76 MB·English

by  Goutam Brahmachari

Editedby
GoutamBrahmachari
BioactiveNaturalProducts
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Editedby
GoutamBrahmachari
Bioactive Natural Products
ChemistryandBiology
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Allthosewhoareworkinggloballywithbioactivenaturalproductsforthecauseof
humanwelfare

XI
Contents
Foreword VII
Preface XXI
AbouttheEditor XXV
ListofContributors XXVII
1 AnOverview 1
GoutamBrahmachari
2 UseofChemicalGenomicstoInvestigatetheMechanismofAction
forInhibitoryBioactiveNaturalCompounds 9
DanielBurnside,HoumanMoteshareie,ImeldaG.Marquez,
MohsenHooshyar,BahramSamanfar,KristinaShostak,KatayounOmidi,
HarryE.Peery,MyronL.Smith,andAshkanGolshani
2.1 Introduction:AntibioticResistanceandtheUseofNaturalProducts
asaSourceforNovelAntimicrobials 9
2.2 ChemicalGeneticsandGenomics 10
2.3 DevelopmentofGDATechnology 11
2.3.1 TheUseofGeneDeletionArrays(GDAs)toInvestigate
MOA 12
2.3.2 ChemicalGeneticInteractions 12
2.3.3 QuantifyingGeneticandChemicalGeneticInteractions 14
2.3.4 DataAnalysis 15
2.3.5 PlatformsforChemicalGenomicGDAStudies 17
2.3.6 WhyScreenNaturalProductsinGDAs? 19
2.3.7 SuccessfulApplicationsofGDATechnology 21
2.4 ConcludingRemarks 22
Abbreviations 24
References 24
XII Contents
3 High-ThroughputDrugScreeningBasedonCancerSignaling
inNaturalProductScreening 33
XinxinZhang,YupingDu,andJinboYang
3.1 Introduction 33
3.2 CancerSignalingPathwayswithTheirOwnDrugScreeningAssays
inHTS 35
3.2.1 β-GalactosidaseEnzymeComplementationAssaysforEGFR
SignalingDrugScreening 35
3.2.2 FluorescenceSuperquenchingAssaysforPI3KsSignalingDrug
Screening 35
3.2.3 TOPFlashReporterGeneAssaysforWntSignalingDrug
Screening 36
3.2.4 LuciferaseReporterGeneAssaysforSTATsSignalingDrug
Screening 37
3.3 ConcludingRemarks 37
Abbreviations 38
References 38
4 Immunosuppressants:RemarkableMicrobialProducts 43
PreetiVaishnav,YoungJ.Yoo,YeoJ.Yoon,andArnoldL.Demain
4.1 Introduction 43
4.2 Discovery 44
4.3 ModeofAction 47
4.4 Biosynthesis 49
4.4.1 Acetate,Propionate,Butyrate,Methionine,andValineas
PrecursorsoftheMacrolideRingsofSirolimus,Ascomycin,and
Tacrolimus 49
4.4.2 PipecolateMoietyoftheMacrolideRingofSirolimus,
Ascomycin,andTacrolimus 52
4.4.3 TheFinalStepinBiosynthesisofAscomycinsand
Tacrolimus 55
4.4.4 FormationoftheSubstitutedCyclohexylMoietyofSirolimus,
Tacrolimus,andAscomycins 58
4.4.5 BiosynthesisofCyclosporin 61
4.5 GeneticsandStrainImprovement 63
4.6 FermentationandNutritionalStudies 65
4.7 OtherActivitiesofImmunosuppressants 69
4.8 ConcludingRemarks 71
Acknowledgments 72
References 72