HOW WILL BIOINFORMATICS INFLUENCE METABOLIC ENGINEERING

Ten microbial genomes have been fully sequenced to date, and the seque ncing of many more genomes is expected to be completed before the end of the century. The assignment of function to open reading frames (ORF s) is progressing, and for some genomes over 70% of functional assignm ents have been made. The majority of the assigned ORFs relate to metab olic functions. Thus, the complete genetic and biochemical functions o f a number of microbial cells may be soon available. From a-metabolic engineering standpoint, these developments open a new realm of possibi lities. Metabolic analysis and engineering strategies can now be built on a sound genomic basis. An important question that now arises; how should these tasks be approached? Flux-balance analysis (FBA) has the potential to play an important role, It is based on the fundamental pr inciple of mass conservation. It requires only the stoichiometric matr ix, the metabolic demands, and same strain specific parameters. import antly, no enzymatic kinetic data is required. in this article, we show how the genomically defined microbial metabolic genotypes can be anal yzed by FBA. Fundamental concepts of metabolic genotype, metabolic phe notype, metabolic redundancy and robustness are defined and examples o f their use given. We discuss the advantage of this approach, and how FBA is expected to find uses in the near future. FBA is likely to beco me an important analysis tool for genomically based approaches to meta bolic engineering, strain design, and development. (C) 1998 John Wiley & Sons, Inc.