title: A unique fungal lysine biosynthesis enzyme shares a common ancestor with tricarboxylic acid cycle and leucine biosynthetic enzymes found in diverse organisms.
abstract: Fungi have evolved a unique alpha-amino-adipate pathway for lysine biosynthesis. The fungal-specific enzyme homoaconitate hydratase from this pathway is moderately similar to the aconitase-family proteins from a diverse array of taxonomic groups, which have varying modes of obtaining lysine. We have used the similarity of homoaconitate hydratase to isopropylmalate isomerase (serving in leucine biosynthesis), aconitase (from the tricarboxylic acid cycle), and iron-responsive element binding proteins (cytosolic aconitase) from fungi and other eukaryotes, eubacteria, and archaea to evaluate possible evolutionary scenarios for the origin of this pathway. Refined sequence alignments show that aconitase active site residues are highly conserved in each of the enzymes, and intervening sequence sites are quite dissimilar. This pattern suggests strong purifying selection has acted to preserve the aconitase active site residues for a common catalytic mechanism; numerous other substitutions occur due to adaptive evolution or simply lack of functional constraint. We hypothesize that the similarities are the remnants of an ancestral gene duplication, which may not have occurred within the fungal lineage. Maximum likelihood, neighbor joining, and maximum parsimony phylogenetic comparisons show that the alpha-aminoadipate pathway enzyme is an outgroup to all aconitase family proteins for which sequence is currently available.
authors.affiliation: Department of Microbiology, Miami University, Oxford, OH 45056, USA. sdi1@cornell.edu
authors.forename: S D
authors.initials: SD
authors.lastname: Irvin
authors.forename: J K
authors.initials: JK
authors.lastname: Bhattacharjee
mesh_terms: D000154:Aconitate Hydratase / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001105:Archaea / Q000201:enzymology / Q000235:genetics; D002952:Citric Acid Cycle; D019143:Evolution, Molecular; D006801:Humans; D006836:Hydro-Lyases / Q000235:genetics*; D007535:Isomerases / Q000235:genetics; D007930:Leucine / Q000096:biosynthesis; D008239:Lysine / Q000096:biosynthesis*; D008969:Molecular Sequence Data; D010802:Phylogeny; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity
chemical_list: D006836:Hydro-Lyases; D000154:Aconitate Hydratase; C032241:isopropylmalate isomerase; C107855:homoaconitate hydratase; D007535:Isomerases; D007930:Leucine; D008239:Lysine