Metabolic engineering challenges in the post-genomic era

Metabolic engineering is a young field, just over ten-years old. During this period, it has developed a well-defined methodology and a focused research portfolio of rich intellectual content and particular relevance to biotechnology and biological engineering. New and diverse opportunities for metabolic engineering emerge quickly in this genomic era. Although the focus (e.g. improving cells) and central components (e.g. assessing cell physiology) of metabolic engineering remain the same, new tools are required to take advantage of the opportunities arising from the availability of whole-genome sequence information. Cellular phenotype is a manifestation of gene expression levels, metabolic demand, resource availability, and cellular stresses. Above all, metabolic function is constrained by the stoichiometry and individual reaction kinetics of the reaction network. To understand the behavior of these systems, the well-established framework of reaction engineering must be complemented with new experimental methods specifically designed for the elucidation of metabolic pathways and bioreaction networks. Most of all, a combination of rational and combinatorial approaches is required to effectively sample and map as much of the metabolic space as possible. The above framework along with important tools of metabolic engineering will be reviewed in this article. We will then show their application to case studies of industrial and medical interest while emphasizing the strong influence and links of metabolic engineering to chemical reaction engineering. (C) 2004 Elsevier Ltd. All rights reserved.