A Rapid, Small-Scale Method for Improving Fermentation Medium Performance

i Acknowledgments iii List of Figures vi List of Tables vii Chapter One: Introduction 1 1.1 Motivation 1 1.2 Objectives 3 1.3 Approach 4 1.4 Overview of the Thesis 4 Chapter Two: Literature Review 6 2.1 Fermentation Technology 6 2.1.1 Aspects of Submerged Culture 6 2.1.2 Types of Bioreactors 7 2.1.3 Operating Modes for Submerged Bioreactors 11 2.2 Fermentation Medium 12 2.2.1 General Review 12 2.2.2 Medium Components 12 2.2.3 Complex Medium 14 2.2.4 Defined Medium 14 2.3 Developing Fermentation Medium 16 2.3.1 Medium Formulation 16 2.3.2 Media Development 17 2.3.3 Experimental Design 18 2.3.4 Optimization Techniques 19 2.3.5 Box-Behnken Design 21 2.4 Metabolite Production Pathway 23 2.4.1 Primary Metabolites 23 2.4.2 Secondary Metabolites 24 2.4.3 Inoculum in Secondary Metabolites 26 2.4.4 Streptomyces hygroscopicus Growth Conditions 28 2.4.5 Rapamycin and the Rapamycin Biosynthetic Pathway 29 2.5 Microtitre Plate 31 2.5.