Modulating transcription through development of semi-synthetic yeast core promoters

Saccharomyces cerevisiae can be used as a platform the production of bulk and fine chemicals, although for this it is necessary to introduce heterologous metabolic pathways and fine-tune gene expression. The latter can be done by regulating transcription, for example by altering the gene’s promoter or terminator.

Eukaryotic promoters are usually composed of a core promoter element, where the RNA polymerase II begins transcription, and upstream regulatory elements. There have been many previous efforts regarding promoter engineering in yeast, for example through hybrid promoter engineering, nucleosome affinity modulation, or through the introduction of heterologous and synthetic inducible transcription factors in from the core promoters. One important trait for yeast engineering is the robustness and reproducibility of promoters, and the use of heterologous regulatory parts is recommended due to the lack of interaction with the host’s native regulation elements.

One of the limitations in S. cerevisiae engineering is the length of its promoters, which can reach hundreds of nucleotides. This could be solved using short viral promoters, although this has several disadvantages, for example the heterologous expression of the T7 RNA polymerase is required. Another option could be the construction of short promoters that are able to interact with the native yeast RNA polymerase II, although there is a risk of homologous recombination between parts.

In this work an alternative strategy is presented, focused on the design and characterization of short (less than 100 nucleotides), constitutive synthetic yeast promotors of different strengths based on the well-characterized TEF1 promoter. For more information check out the paper recently published by Decoene et al. in PLoS ONE.

Decoene T, De Maeseneire SL, De Mey M (2019). Modulating transcription through development of semi-synthetic yeast core promoters. PLoS ONE 14(11): e0224476.

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