Abstract
BackgroundThe biosynthesis of leucine is a biochemical pathway common to prokaryotes, plants and fungi, but absent from humans and animals. The pathway is a proposed target for antimicrobial therapy.Methodology/Principal FindingsHere we identified the leuA gene encoding α-isopropylmalate synthase in the zygomycete fungus Phycomyces blakesleeanus using a genetic mapping approach with crosses between wild type and leucine auxotrophic strains. To confirm the function of the gene, Phycomyces leuA was used to complement the auxotrophic phenotype exhibited by mutation of the leu3+ gene of the ascomycete fungus Schizosaccharomyces pombe. Phylogenetic analysis revealed that the leuA gene in Phycomyces, other zygomycetes, and the chytrids is more closely related to homologs in plants and photosynthetic bacteria than ascomycetes or basidiomycetes, and suggests that the Dikarya have acquired the gene more recently.Conclusions/SignificanceThe identification of leuA in Phycomyces adds to the growing body of evidence that some primary metabolic pathways or parts of them have arisen multiple times during the evolution of fungi, probably through horizontal gene transfer events.
Highlights
Many microbes are capable of growth under diverse conditions due to their ability to utilize whatever nutrients are available and produce de novo metabolites that are essential for life
Leucine biosynthesis is required for full virulence in a fungal model of disease using a pathogenic isolate of Saccharomyces cerevisiae [4]
The second contig (#15) was examined for candidates for the ribC and leuA genes. Candidates for both genes were identified: ribC as a putative RNA pseudouridylate synthase and leuA as a putative a-isopropylmalate synthase (a-IPMS). aisopropylmalate synthase catalyzes the first step in the biosynthesis of leucine from acetyl-CoA and a-ketoisovalerate
Summary
Many microbes are capable of growth under diverse conditions due to their ability to utilize whatever nutrients are available and produce de novo metabolites that are essential for life This contrasts to animal species that rely on acquiring many basic metabolites, such as the essential amino acids, from food. In the yeast S. cerevisiae there is a complex system of control in which at least four inputs regulate pathway output This includes allosteric inhibition by leucine on the first enzyme of the pathway, a-isopropylmalate synthase (aIPMS), to control its enzymatic activity [12,13]. The biosynthesis of leucine is a biochemical pathway common to prokaryotes, plants and fungi, but absent from humans and animals.
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