The primordial metabolism: an ancestral interconnection between leucine, arginine, and lysine biosynthesis

Abstract

Background: It is generally assumed that primordial cells had small genomes with simple genes coding for enzymes able to react with a wide range of chemically related substrates, interconnecting different metabolic routes. New genes coding for enzymes with a narrowed substrate specificity arose by paralogous duplication(s) of ancestral ones and evolutionary divergence. In this way new metabolic pathways were built up by primordial cells. Useful hints to disclose the origin and evolution of ancestral metabolic routes and their interconnections can be obtained by comparing sequences of enzymes involved in the same or different metabolic routes. From this viewpoint, the lysine, arginine, and leucine biosynthetic routes represent very interesting study-models. Some of the lys, arg and leu genes are paralogs; this led to the suggestion that their ancestor genes might interconnect the three pathways. The aim of this work was to trace the evolutionary pathway leading to the appearance of the extant biosynthetic routes and to try to disclose the interrelationships existing between them and other pathways in the early stages of cellular evolution.

Evolution and Multifarious Horizontal Transfer of an Alternative Biosynthetic Pathway for the Alternative Polyamine sym-Homospermidine

“…The metabolic routes for lysine (diaminopimelate and ␣-aminoadipate pathway) and arginine biosynthesis are represented along with bifurcating pathways that stem from various metabolic intermediates (NAD biosynthesis from aspartate, threonine/methionine biosynthesis from aspartate ␤-semialdehyde, and polyamine biosynthesis from putrescine/aspartate ␤-semialdehyde). Enzymes with similar folds are indicated with similarly colored circles, and pathways with similar consecutive enzymes that are presumed to stem from a common ancestral pathway (78) are boxed in dashed lines. Genes encoding GAPDH-like folds are labeled in red and numbered according to three general groups of structural similarity.…”

“…8); one belongs to an alternative lysine biosynthetic pathway from aminoadipate (N-acetyl-␥-aminoadipyl-phosphate reductase), whereas the other participates in arginine biosynthesis (N-acetyl-␥-glutamylphosphate reductase (PDB: 1xyg)). Indeed, the four main genes belonging to the two pathways to lysine biosynthesis (diaminopimelate and ␣-aminoadipate pathways) and the pathway to arginine biosynthesis are thought to have evolved from paralogous duplications followed by evolutionary divergence (78). Of note, the close HSS homologue, CANSDH, brings together a side product of arginine biosynthesis (putrescine) with the intermediate common to the lysine (diaminopimelate pathway), methionine, and threonine biosynthetic pathways (aspartate ␤-semialdehyde) to form spermidine.…”

New insights into the regulatory networks of paralogous genes in bacteria

“…By identifying the differences in the assigned biochemical reaction or metabolic pathway, we were able to show that 198 (42 %) of the paralogous groups in E. coli have a known metabolic function, according to the KEGG database (Gu et al, , 2002Kanehisa et al, 2008). From this set, we identified 53 groups (27 %) that possess members which share the same metabolic pathway genes, but may also involve large parts of metabolic pathways, as is the case with the leucine, arginine and lysine biosynthesis pathways, where several enzymes are involved in related chemical reactions, with analogous but different substrates (Fondi et al, 2007).…”

“…Slightly different tendencies were observed in the 485 groups of paralogous genes in B. subtilis. Finally, duplication events may not be restricted to individual genes, but may also involve large parts of metabolic pathways, as is the case with the leucine, arginine and lysine biosynthesis pathways, where several enzymes are involved in related chemical reactions, with analogous but different substrates (Fondi et al, 2007).…”

“…By identifying the differences in the assigned biochemical reaction or metabolic pathway, we were able to show that 198 (42 %) of the paralogous groups in E. coli have a known metabolic function, according to the KEGG database (Gu et al, , 2002Kanehisa et al, 2008). From this set, we identified 53 groups (27 %) that possess members which share the same metabolic pathway genes, but may also involve large parts of metabolic pathways, as is the case with the leucine, arginine and lysine biosynthesis pathways, where several enzymes are involved in related chemical reactions, with analogous but different substrates (Fondi et al, 2007).Alternative sigma, anti-sigma and anti-anti-sigma factors may also be part of the regulatory network of paralogous genesTranscription regulation by alternative sigma factors, antisigma factors and anti-anti-sigma factors is a common strategy used by various organisms in order to accomplish different cellular processes, including (i) the regulation of specific biogenesis processes, such as flagellar biosynthesis in E. coli, which is regulated by s 28 (Chilcott & Hughes, 2000); (ii) the response to a metabolic requirement, as occurs when E. coli grows in nitrogen-deprived conditions and gene transcription depends on s 54 (Reitzer & Schneider, 2001); (iii) the response to different kinds of stress factors, as in heat shock stress in E. coli, which is regulated by s 32 , or in the case of general stress in B. subtilis, which is regulated by s B (Hecker et al, 2007); (iv) synchronized transcription at a specific growth stage, as occurs in the stationary phase of E. coli, where transcription is regulated by s 38 (Hengge-Aronis, 2002); and (v) coordinated cell differentiation processes, such as B. subtilis forespore formation, whose regulation depends on genes transcribed by s E , s , 2000). Although in general each of the sigma factors recognizes clearly distinguishable promoter sequences and thus transcribes different groups of genes, in E. coli the stationary-phase s 38 and its paralogous counterpart, the housekeeping s…”