Abstract
Xanthophyllomyces dendrorhous is a basidiomycete yeast known as a natural producer of astaxanthin, a carotenoid of commercial interest because of its antioxidant properties. Recent studies indicated that X. dendrorhous has a functional SREBP pathway involved in the regulation of isoprenoid compound biosynthesis, which includes ergosterol and carotenoids. SREBP is a major regulator of sterol metabolism and homeostasis in mammals; characterization in fungi also provides information about its role in the hypoxia adaptation response and virulence. SREBP protease processing is required to activate SREBP pathway functions in fungi. Here, we identified and described the STP1 gene, which encodes a metallopeptidase of the M50 family involved in the proteolytic activation of the transcription factor Sre1 of the SREBP pathway, in X. dendrorhous We assessed STP1 function in Δstp1 strains derived from the wild-type and a mutant of ergosterol biosynthesis that overproduces carotenoids and sterols. Bioinformatic analysis of the deduced protein predicted the presence of characteristic features identified in homologs from mammals and fungi. The Δstp1 mutation decreased yeast growth in the presence of azole drugs and reduced transcript levels of Sre1-dependent genes. This mutation also negatively affected the carotenoid- and sterol-overproducing phenotype. Western blot analysis demonstrated that Sre1 was activated in the yeast ergosterol biosynthesis mutant and that the Δstp1 mutation introduced in this strain prevented Sre1 proteolytic activation. Overall, our results demonstrate that STP1 encodes a metallopeptidase involved in proteolytic activation of Sre1 in X. dendrorhous, contributing to our understanding of fungal SREBP pathways.
Highlights
Xanthophyllomyces dendrorhous is a basidiomycete yeast known as a natural producer of astaxanthin, a carotenoid of commercial interest because of its antioxidant properties
We identified and described a new gene involved in the SREBP pathway of the carotenogenic yeast X. dendrorhous
The identified STP1 gene is homologous to genes encoding the site-2 protease (S2P) protease in H. sapiens and Stp1 in C. neoformans, which are required for proteolytic activation of the transcription factor SREBP/Sre1
Summary
Xanthophyllomyces dendrorhous is a basidiomycete yeast known as a natural producer of astaxanthin, a carotenoid of commercial interest because of its antioxidant properties. We identified and described the STP1 gene, which encodes a metallopeptidase of the M50 family involved in the proteolytic activation of the transcription factor Sre of the SREBP pathway, in X. dendrorhous. The stp mutation decreased yeast growth in the presence of azole drugs and reduced transcript levels of Sre1-dependent genes. This mutation negatively affected the carotenoid- and sterol-overproducing phenotype. Our results demonstrate that STP1 encodes a metallopeptidase involved in proteolytic activation of Sre in X. dendrorhous, contributing to our understanding of fungal SREBP pathways.—Gómez, M., M. One of the major mechanisms regulating sterol metabolism and homeostasis in mammalian cells is the SREBP pathway (Fig. 1), which uses a family of ER membranebound transcription factors called SREBPs [1].
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