ABSTRACT
SINCE JACOB AND MONOD DISCOVERED the regulation of lactose operon half a century ago, many modes of regulation have been discovered (Pardee, Jacob, and Monod, 1959). Like other intracellular events, metabolism is regulated at various levels ranging from transcriptional initiation to metabolite feedback inhibition. ese regulations are evolved to control the timing and extent of metabolic ux to dierent branches in order to supply building blocks, reducing power, cofactors, and
energy needed for cell growth, maintenance, and adaptation to environmental changes. Because of these control systems, the cells are able to counter genetic or environmental changes that attempt to alter metabolic ux. As such, regulation is the most important issue that a metabolic engineer must deal with. Indeed, random mutagenesis that destroys regulation was the earliest tool of metabolic engineering for production of amino acids. Among dierent forms of regulation, the most common and best understood is transcriptional regulation. Because of its modularity, transcriptional regulation is readily amenable to engineering. is section deals with three aspects of bacterial transcriptional regulation: regulation of primary metabolism, regulation of secondary metabolism, and engineering of synthetic regulatory networks. Other forms of regulation, such as enzyme activity modulation, are certainly important, but tools for systematic engineering of these mechanisms remain to be developed.
