The biochemical pathway for biosynthesis of aromatic amino acids is widespread in prokaryotes, eukaryotic microorganisms, and in higher plants but is absent in mammalian organisms. Therefore, the multiplicity of enzymes that are utilized by this pathway are apt targets for the design of antimicrobial and herbicidal compounds, which have no target in man and other mammals. Furthermore, there is an increasing recognition of the enormous diversity between organisms with respect to the details of aromatic metabolism and the context of interface with other metabolic networks. Thus, there are many possibilities for selective approaches against pathogens that will not harm beneficial microorganisms. In addition, the metabolism of aromatic compounds in nature is of particular interest to man because it is a source of numerous natural products that are useful (e.g., antibiotics, pigments, etc.) or harmful (e.g., toxins). Two manuscripts will be prepared that elucidate in scholarly and comprehensive detail the biochemical mechanisms and enzymological features of aromatic metabolism. The latter information will be integrated into a comparative and evolutionary context and will be guided by a genomic and bioinformatic perspective. A nomenclature will be developed that has a rational basis and is suitable for comparative analysis. A larger gestalt of metabolic networking will be elucidated by inclusion of interlocking biochemical pathways, e.g., the direct relationship between sedne and tryptophan synthesis, as well as the more remote relationships that also include folate biosynthesis (via 4-aminobenzoate), pyridoxine biosynthesis, and histidine biosynthesis. A web site will be created to allow public access to the information and analysis as it is organized and will be designed to facilitate a long-term process that at maturation in 3 years will justify a long-term objective of securing a database that can be maintained, improved and progressively expanded to other metabolic networks.
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| Xie, Gary; Bonner, Carol A; Song, Jian et al. (2004) Inter-genomic displacement via lateral gene transfer of bacterial trp operons in an overall context of vertical genealogy. BMC Biol 2:15 |
