title: Deficiency in frataxin homologue YFH1 in the yeast Pichia  guilliermondii leads to missregulation of iron acquisition  and riboflavin biosynthesis and affects sulfate assimilation.
abstract: Pichia guilliermondii is a representative of yeast species that overproduce riboflavin (vitamin B2) in response to iron deprivation. P. guilliermondii YFH1 gene coding for frataxin homologue, eukaryotic mitochondrial protein involved in iron trafficking and storage, was identified and deleted. Constructed P. guilliermondii Δyfh1 mutant grew very poorly in a sucrose-containing synthetic medium supplemented with sulfate or sulfite as a sole sulfur source. Addition of sodium sulfide, glutathione, cysteine, methionine, N-acetyl-L-cysteine partially restored growth rate of the mutant suggesting that it is impaired in sulfate assimilation. Cellular iron content in Δyfh1 mutant was ~3-3.5 times higher as compared to the parental strain. It produced 50-70 times more riboflavin in iron sufficient synthetic media relative to the parental wildtype strain. Biomass yield of the mutant in the synthetic glutathione containing medium supplemented with glycerol as a sole carbon source was 1.4- and 2.6-fold increased as compared to sucrose and succinate containing media, respectively. Oxygen uptake of the Δyfh1 mutant on sucrose, glycerol or succinate, when compared to the parental strain, was decreased 5.5-, 1.7- and 1.5-fold, respectively. Substitution of sucrose or glycerol in the synthetic iron sufficient medium with succinate completely abolished riboflavin overproduction by the mutants. Deletion of the YFH1 gene caused hypersensitivity to hydrogen peroxide and exogenously added riboflavin and led to alterations in superoxide dismutase activities. Thus, deletion of the gene coding for yeast frataxin homologue has pleiotropic effect on metabolism in P. guilliermondii.
authors: Institute of Cell Biology, NAS of Ukraine, Drahomanov Street 14/16, 79005 Lviv, Ukraine.
authors: Yuriy V
authors: YV
authors: Pynyaha
authors: Yuriy R
authors: YR
authors: Boretsky
authors: Daria V
authors: DV
authors: Fedorovych
authors: Lubov R
authors: LR
authors: Fayura
authors: Andriy I
authors: AI
authors: Levkiv
authors: Vira M
authors: VM
authors: Ubiyvovk
authors: Olha V
authors: OV
authors: Protchenko
authors: Caroline C
authors: CC
authors: Philpott
authors: Andriy A
authors: AA
authors: Sibirny
mesh_terms: D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D005990:Glycerol / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D017136:Ion Transport / Q000187:drug effects / Q000235:genetics; D007501:Iron / Q000378:metabolism*; D033862:Iron-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D030781:Organisms, Genetically Modified / Q000235:genetics / Q000378:metabolism*; D010843:Pichia / Q000235:genetics / Q000378:metabolism*; D012256:Riboflavin / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D019802:Succinic Acid / Q000378:metabolism; D013395:Sucrose / Q000378:metabolism; D013457:Sulfur Compounds / Q000378:metabolism; D013463:Sulfuric Acid Esters / Q000378:metabolism; D013482:Superoxide Dismutase / Q000032:analysis; D000096923:Frataxin
chemical_list: D005656:Fungal Proteins; D005990:Glycerol; D006861:Hydrogen Peroxide; D007501:Iron; D033862:Iron-Binding Proteins; D012256:Riboflavin; D019802:Succinic Acid; D013395:Sucrose; D013457:Sulfur Compounds; D013463:Sulfuric Acid Esters; D013482:Superoxide Dismutase; D000096923:Frataxin