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Investigating the role of the transcriptional regulator Ure2 on the metabolism of Saccharomyces cerevisiae: a multi-omics approach

Ure2 regulates nitrogen catabolite repression in Saccharomyces cerevisiae. Deletion of URE2 induces a physiological state mimicking the nitrogen starvation and autophagic responses. Previous work has shown that deletion of URE2 increases the fermentation rate of some wine-producing strains of S. cerevisiae. In this work, we investigated the effect of URE2 deletion (ΔURE2) on the metabolism of S. cerevisiae. During growth on glucose, the ΔURE2 mutant grew less well than the wild type; however, it produced ethanol at higher rates. To better under the behavior of this mutant, we performed transcriptomics and metabolomics. Analysis of the RNA sequencing results and metabolite levels indicate that the mutant strain exhibited characteristics of both nitrogen starvation and autophagy. In addition, many pyruvate decarboxylase and alcohol dehydrogenase isoforms were expressed at higher rates than the wild type. The mutant also accumulated less trehalose and glycogen, and produced more lipids. These results suggest that URE2 may be a promising target for metabolic engineering in S. cerevisiae and potentially other strains of yeast as well for the production of lipid-based fuels and chemicals.

59 BASIC BIOLOGICAL SCIENCES↗

Materials Data on URe2 by Materials Project

URe2 is Hexagonal Laves structured and crystallizes in the orthorhombic Cmcm space group. The structure is three-dimensional. U is bonded in a 10-coordinate geometry to one U and twelve Re atoms. The U–U bond length is 2.66 Å. There are a spread of U–Re bond distances ranging from 3.06–3.28 Å. There are three inequivalent Re sites. In the first Re site, Re is bonded to six equivalent U and six Re atoms to form a mixture of edge, face, and corner-sharing ReU6Re6 cuboctahedra. There are two shorter (2.63 Å) and four longer (2.64 Å) Re–Re bond lengths. In the second Re site, Re is bonded to six equivalent U and six Re atoms to form a mixture of edge, face, and corner-sharing ReU6Re6 cuboctahedra. There are a spread of Re–Re bond distances ranging from 2.67–2.85 Å. In the third Re site, Re is bonded to six equivalent U and six Re atoms to form a mixture of edge, face, and corner-sharing ReU6Re6 cuboctahedra.

36 MATERIALS SCIENCE↗

Materials Data on URe2 by Materials Project

URe2 is Frank-Kasper $\mu$ Phase-like structured and crystallizes in the orthorhombic Cmcm space group. The structure is three-dimensional. U is bonded in a 8-coordinate geometry to two equivalent U and twelve Re atoms. There are one shorter (2.77 Å) and one longer (3.19 Å) U–U bond lengths. There are a spread of U–Re bond distances ranging from 2.99–3.35 Å. There are three inequivalent Re sites. In the first Re site, Re is bonded to six equivalent U and six Re atoms to form a mixture of edge, corner, and face-sharing ReU6Re6 cuboctahedra. There are two shorter (2.60 Å) and four longer (2.67 Å) Re–Re bond lengths. In the second Re site, Re is bonded to six equivalent U and six Re atoms to form a mixture of edge, corner, and face-sharing ReU6Re6 cuboctahedra. There are two shorter (2.57 Å) and two longer (2.78 Å) Re–Re bond lengths. In the third Re site, Re is bonded to six equivalent U and six Re atoms to form a mixture of distorted edge, corner, and face-sharing ReU6Re6 cuboctahedra. There are one shorter (2.90 Å) and one longer (2.98 Å) Re–Re bond lengths.

36 MATERIALS SCIENCE↗

raogroupuiuc/scer_ure2

Data repository for the S. cerevisiae ure2 deletion project Project: Investigating the role of the transcriptional regulator Ure2 on the metabolism of Saccharomyces cerevisiae: a multi-omics approach. Key points • Deletion of URE2 increases ethanol and lipid production in Saccharomyces cerevisiae. • Deletion of URE2 reduces glycogen and trehalose production. • Metabolic changes mimic nitrogen starvation and autophagic response.

Deewan, Anshu↗