Contents

6.1 Introduction 89

6.2 Historical Perspective 91

6.3 Antibiotics 92

6.4 Screening 94

6.4.1 General Concepts 94

6.4.2 Whole Organism Screening 95

6.4.3 Target-Based Screening 96

6.4.4 Dereplication 97

6.4.5 Screening Improvements 97

6.5 Optimization of Natural Product Leads 99

6.5.1 Semisynthesis 99

6.5.2 Improvements in Natural Products through Total Synthesis 100

6.5.3 Biosynthetic Modifications 100

6.5.3.1 Mutasynthesis 101

6.5.3.2 Polyketide Synthase (PKS) Engineering 101

6.5.4 Structure-Activity Relationships 103

6.6 Concluding Remarks 105

Further Readings 105

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