Detection and Expression of Biosynthetic Genes in Actinobacteria ...

___________________________________________________________________________________Table of ContentsDeclarations ______________________________________________________iAcknowledgements _________________________________________________iiAbstract __________________________________________________________iiiList of Figures _____________________________________________________vList of Tables _____________________________________________________viiList of Abbreviations _______________________________________________xAims of project, experimental objectives, null hypothesis _________________xiiChapter 1: IntroductionSection 1: General Aspects of Actinobacteria __________________________ 11.1.1 Description of genetic, biochemical and morphological features ofActinobacteria _______________________________________________ 11.1.2 Industrial Relevance of Actinobacteria ____________________________ 11.1.3 Sources of Actinobacterial Secondary Metabolite Diversity ____________ 21.1.4 Evolution of biosynthetic pathways and their relation to secondarymetabolite production _________________________________________ 31.1.5 Classification of Actinobacteria __________________________________ 31.1.6 Actinobacterial Genetic Diversity and Drug Discovery ________________ 41.1.7 Activities of Actinobacteria in the natural habitat ____________________ 4Section 2: Biology of Secondary Metabolism and the Discoveryof Secondary Metabolites in Actinobacteria____________________ 51.2.1 Microbial secondary metabolism __________________________________ 51.2.1.1 Secondary metabolite production ______________________________ 51.2.1.2 Functions of Secondary Metabolites ____________________________ 61.2.1.3 Resistance Mechanisms and Secondary Metabolite Secretion ________ 61.2.2 Microbial Screening for Secondary Metabolites ______________________ 71.2.2.1 Rapid identification of microbial metabolites_____________________ 91.2.2.2 Chemical screening using chromatography and spectroscopy ________ 9Section 3: Secondary Metabolites Produced by Actinobacteria_____________111.3.1 General Aspects of Polyketides __________________________________111.3.1.1 Polyketide Biosynthesis Pathway ______________________________131.3.1.2 Polyketide Synthases (PKS) __________________________________141.3.1.3 Biosynthetic Genes Clusters of Type I Polyketide Synthases ________141.3.1.4 Biosynthetic Gene Clusters of Type II Polyketide Synthases ________161.3.2 Biosynthesis of Deoxysugar Aminoglycoside Antibiotics ______________191.3.2.1 Aminoglycoside Deoxysugar Biosynthetic Genes in Actinobacteria ___201.3.3 β-Lactam Antibiotics ___________________________________________211.3.3.1 β-lactam biosynthetic genes ___________________________________22Section 4: Gene expression in Actinobacteria ___________________________241.4.1 Regulation of Gene Expression in Actinobacteria______________________241.4.1.1 Transcription_______________________________________________25___________________________________________________________________________________