Molecular Evolution of the Lysine Biosynthetic Pathways

Abstract

Among the different biosynthetic pathways found in extant organisms, lysine biosynthesis is peculiar because it has two different anabolic routes. One is the diaminopimelic acid pathway (DAP), and the other over the a-aminoadipic acid route (AAA). A variant of the AAA route that includes some enzymes involved in arginine and leucine biosyntheses has been recently reported in Thermus thermophilus (Nishida et al. 1999). Here we describe the results of a detailed genomic analysis of each of the sequences involved in the two lysine anabolic routes, as well as of genes from other routes related to them. No evidence was found of an evolutionary relationship between the DAP and AAA enzymes. Our results suggest that the DAP pathway is related to arginine metabolism, since the lysC, asd, dapC, dapE, and lysA genes from lysine biosynthesis are related to the argB, argC, argD, argE, and speAC genes, respectively, whose products catalyze different steps in arginine metabolism. This work supports previous reports on the relationship between AAA gene products and some enzymes involved in leucine biosynthesis and the tricarboxylic acid cycle (Irvin and Bhattacharjee 1998; Miyazaki et al. 2001). Here we discuss the significance of the recent finding that several genes involved in the arginine (Arg) and leucine (Leu) biosynthesis participate in a new alternative route of the AAA pathway (Miyazaki et al. 2001). Our results demonstrate a clear relationship between the DAP and Arg routes, and between the AAA and Leu pathways.

Parallel genomic evolution and metabolic interdependence in an ancient symbiosis

“…As observed in Escherichia coli, we predict that the DapC activity in lysine biosynthesis is fulfilled by ArgD (13). The lysine and arginine pathways show evolutionary homology (14), and one Sulcia gene cannot be definitely assigned as either argE or dapE. These two homologous enzymes perform the same chemical reaction (the cleavage of an amide bond) on related molecules, and this one gene may perform both roles in Sulcia.…”

Superessential reactions in metabolic networks

“…1.7], the final enzyme involved in the production of m-DAP, is actively being explored as a drug target (63)(64)(65)(66). Although DAP epimerase is essential for growth on all 54 carbon sources in E. coli, it is essential only in 54.2% of random viable networks, because many microbes can synthesize m-DAP through dia-minopimelate dehydrogenase (EC 1.4.1.16) (67). In other words, inhibition of this enzyme could be ineffective in the long run, because there is a known route of resistance.…”

Aspartate-Derived Amino Acid Biosynthesis inArabidopsis thaliana

“…Although most prokaryotes also synthesize lysine from m-diaminopimelate, the metabolic pathways leading from tetrahydrodipicolinate to m-diaminopimelate are distinct from the one found in A. thaliana (Hudson et al, 2006). Yet another, completely different pathway for lysine biosynthesis exists in Saccharomyces cerevisiae and most fungi, where L-2-diaminoadipate rather than L-aspartate-4-semialdehyde is the precursor for lysine biosynthesis (Velasco et al, 2002). Therefore, lysine is not an aspartatederived amino acid in S. cerevisiae.…”