Two Origins for the Gene Encoding α-Isopropylmalate Synthase in Fungi

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.

Regulation of the NADP-glutamate dehydrogenase gene gdhA in Aspergillus nidulans by the Zn(II)2Cys6 transcription factor LeuB

“…same common ancestor (Larson & Idnurm, 2010). LeuC has a C-terminal extension absent in both Leu4p and Leu9p.…”

A New Genetic Linkage Map of the Zygomycete Fungus Phycomyces blakesleeanus

“…Genes that have been sequenced and also mapped based on mutant phenotypes in Phycomyces are: carRA and carB that control biosynthesis of β-carotene [45], [46]; the sex mating type locus [39]; madA and madB that encode a blue light photoreceptor complex [35], [36]; leuA and purC that are linked auxotrophic markers [47]; pyrG [26], [48]; and recently carS for cleavage of β-carotene [49], [50]. Knowledge of other genes would help link the two maps more thoroughly.…”

“…For mapping mutations to parts of the chromosome, bulked segregant analysis and genome resequencing could be used, as has been successful for mapping in Neurospora crassa [61]. We have already applied these PCR-RFLPs for map-based identication of four genes, carS , leuA , madC and madI , and narrowing the DNA regions for others ([47], [49] and unpublished data). The identification of the furA , lysA and nicA genes adjacent to madD , madE and carC genes, respectively, should facilitate the identification of genes required for phototropism and biosynthesis of β-carotene.…”

Development of resources for the analysis of gene function in Pucciniomycotina red yeasts

“…This gene encodes the first enzyme dedicated to the biosynthesis of leucine. Previous research on the evolution of this gene in the fungal kingdom demonstrated two distinct groups, one found in the Dikarya species and the other in the basal non-Dikarya fungi (Larson and Idnurm, 2010). However, the function of the gene in the basidiomycetes had not been assessed by gene mutation.…”

“…The rationale behind targeting LEU1 was threefold. First, homologs were under investigation in a zygomycete and ascomycete in the laboratory for understanding LEU1 evolution in the fungal kingdom (Larson and Idnurm, 2010), and the Sporobolomyces sp. mutation would provide experimental evidence for the function of this form of the gene in leucine biosynthesis within the basidiomycetes.…”