Scientific methods of enhancing gene expression including genomics, applied molecular biology, metabolic engineering, and combinatorial biosynthesis have been sufficiently developed to make a major impact on recombinant protein production. However, it appears that the combination of trial-and-error experimentation and molecular biology are not sufficient to design an optimum strategy to reach the goal. This book provides a thorough coverage of theoretical and design aspects of two engineering methodologies to overcome this shortcoming. Special emphasis was placed on the effect of the fermentation medium components of A.niger on a recombinant protein production. Statistically based experimental designs in a sequential manner were introduced as powerful tools and applied for medium optimization. A detailed metabolic network comprising intracellular compartments, amino acid catabolism and experimental flux measurements of the key metabolites should be developed and used for optimization purposes. The proposed strategy should be useful to professionals in the field of biotechnology who seek to understand the response of microorganisms to environmental stimuli.