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A single Gal4-like transcription factor activates the Crabtree effect in Komagataella phaffii.

ABSTRACT: The Crabtree phenotype defines whether a yeast can perform simultaneous respiration and fermentation under aerobic conditions at high growth rates. It provides Crabtree positive yeasts an evolutionary advantage of consuming glucose faster and producing ethanol to outcompete other microorganisms in sugar rich environments. While a number of genetic events are associated with the emergence of the Crabtree effect, its evolution remains unresolved. Here we show that overexpression of a single Gal4-like transcription factor is sufficient to convert Crabtree-negative Komagataella phaffii (Pichia pastoris) into a Crabtree positive yeast. Upregulation of the glycolytic genes and a significant increase in glucose uptake rate due to the overexpression of the Gal4-like transcription factor leads to an overflow metabolism, triggering both short-term and long-term Crabtree phenotypes. This indicates that a single genetic perturbation leading to overexpression of one gene may have been sufficient as the first molecular event towards respiro-fermentative metabolism in the course of yeast evolution.

SUBMITTER: Ata O

PROVIDER: S-EPMC6249229 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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A single Gal4-like transcription factor activates the Crabtree effect in Komagataella phaffii.

Ata Özge Ö Rebnegger Corinna C Tatto Nadine E NE Valli Minoska M Mairinger Teresa T Hann Stephan S Steiger Matthias G MG Çalık Pınar P Mattanovich Diethard D

Nature communications 20181121 1

The Crabtree phenotype defines whether a yeast can perform simultaneous respiration and fermentation under aerobic conditions at high growth rates. It provides Crabtree positive yeasts an evolutionary advantage of consuming glucose faster and producing ethanol to outcompete other microorganisms in sugar rich environments. While a number of genetic events are associated with the emergence of the Crabtree effect, its evolution remains unresolved. Here we show that overexpression of a single Gal4-l ...[more]

PMID: 30464212

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Project description:The transcription factors Cat8 and Sip4 were described in Saccharomyces cerevisiae and Kluyveromyces lactis to have very similar DNA binding domains and to be necessary for derepression of a variety of genes under non-fermentative growth conditions via binding to the carbon source responsive elements (CSREs). The methylotrophic yeast Komagataella phaffii (syn Pichia pastoris) has two transcription factors (TFs), which are putative homologs of Cat8 based on sequence similarity, termed Cat8-1 and Cat8-2. It is yet unclear in which cellular processes they are involved and if one of them is actually the homolog of Sip4. To study the roles of the Cat8 homologs in K. phaffii, overexpression or deletion strains were generated for the two TFs. The ability of these mutant strains to grow on different carbon sources was tested, and transcript levels of selected genes from the carbon metabolism were quantified. Our experiments showed that the TFs are required for the growth of K. phaffii on C2 carbon sources, but not on glucose, glycerol or methanol. K. phaffii deleted for Cat8-1 showed impaired growth on acetate, while both Cat8-1 and Cat8-2 are involved in the growth of K. phaffii on ethanol. Correspondingly, both TFs are participating in the activation of ADH2, ALD4 and ACS1, three genes encoding enzymes important for the assimilation of ethanol. Different from S. cerevisiae and K. lactis, Cat8-1 is not regulating the transcription of the putative Sip4-family member Cat8-2 in K. phaffii. Furthermore, Cat8-1 is necessary for the activation of genes from the glyoxylate cycle, whereas Cat8-2 is necessary for the activation of genes from the carnitine shuttle. Neither Cat8-1 nor Cat8-2 are required for the activation of gluconeogenesis genes. Finally, the CAT8-2 gene is repressed by the Mig1-2 transcription factor on glucose and autorepressed by the Cat8-2 protein on all tested carbon sources. Our study identified the involvement of K. phaffii Cat8-1 and Cat8-2 in C2-metabolism, and highlighted similarities and differences to their homologs in other yeast species.

Dataset Information

A single Gal4-like transcription factor activates the Crabtree effect in Komagataella phaffii.

Publications

A single Gal4-like transcription factor activates the Crabtree effect in Komagataella phaffii.

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