INTRODUCTION

Optimization of yield and productivity has been a major goal since the very beginnings of industrial citric acid production. The first significant step in this regard is to be credited to Currie (1916, 1917), who observed that a large number of black Aspergillus strains were very active in the production of citric acid. With his extensive studies of culture media for the mold and his advances toward competitive production of citric acid through fermentation, Currie may also be considered the originator of efforts toward optimizing the biotechnological production process. In fact, Currie's success allowed the United States to become self-sufficient and even to export citric acid to Europe. Since Currie's seminal work, probably a thousand or more scientific studies have been published and several hundred patents issued.

Today, we are at a threshold of further significant improvements. The widespread accessibility of recombinant DNA technology and the possibility of altering phenotypes in specific directions and magnitudes are creating novel and powerful means of microbial manipulation (Archer, MacKenzie, and Jeenes 2001; Harwood and Wipat 2001). Combined with effective mathematical methods, these experimental tools are poised to propel microbial biotechnology to a new level of success. Mathematical guidance is necessary, because it is often no longer sufficient to overexpress the gene of one “rate-limiting” step. Instead, several molecular changes have to be introduced simultaneously and sometimes in very specific proportions, if any real improvements in yield or productivity are to be obtained.