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Deficiency in frataxin homologue YFH1 in the yeast Pichia guilliermondii leads to missregulation of iron acquisition and riboflavin biosynthesis and affects sulfate assimilation

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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 wild-type 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.

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Acknowledgments

This work was supported by CRDF Grant UKB1-2810-LV-06.

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Authors and Affiliations

  1. Institute of Cell Biology, NAS of Ukraine, Drahomanov Street 14/16, 79005, Lviv, Ukraine

    Yuriy V. Pynyaha, Yuriy R. Boretsky, Daria V. Fedorovych, Lubov R. Fayura, Andriy I. Levkiv, Vira M. Ubiyvovk & Andriy A. Sibirny

  2. Liver Diseases Branch, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Building 10, Room 9B-16, 10 Center Drive, Bethesda, MD, 20892-1800, USA

    Olha V. Protchenko & Caroline C. Philpott

  3. Rzeszów University, Ćwiklińskiej 2, 35-601, Rzeszów, Poland

    Andriy A. Sibirny

Authors
  1. Yuriy V. Pynyaha
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  2. Yuriy R. Boretsky
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  3. Daria V. Fedorovych
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  4. Lubov R. Fayura
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  5. Andriy I. Levkiv
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  6. Vira M. Ubiyvovk
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  7. Olha V. Protchenko
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  8. Caroline C. Philpott
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  9. Andriy A. Sibirny
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Correspondence to Andriy A. Sibirny.

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Pynyaha, Y.V., Boretsky, Y.R., Fedorovych, D.V. et al. Deficiency in frataxin homologue YFH1 in the yeast Pichia guilliermondii leads to missregulation of iron acquisition and riboflavin biosynthesis and affects sulfate assimilation. Biometals 22, 1051–1061 (2009). https://doi.org/10.1007/s10534-009-9256-x

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  • DOI: https://doi.org/10.1007/s10534-009-9256-x

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