Advances in the dynamic control of metabolic pathways in Saccharomyces cerevisiae

Abstract

The metabolic engineering of Saccharomyces cerevisiae has great potential for enhancing the production of high-value chemicals and recombinant proteins. Recent studies have demonstrated the effectiveness of dynamic regulation as a strategy for optimizing metabolic flux and improving production efficiency. In this review, we provide an overview of recent advancements in the dynamic regulation of S. cerevisiae metabolism. Here, we focused on the successful utilization of transcription factor (TF)-based biosensors within the dynamic regulatory network of S. cerevisiae. These biosensors are responsive to a wide range of endogenous and exogenous signals, including chemical inducers, light, temperature, cell density, intracellular metabolites, and stress. Additionally, we explored the potential of omics tools for the discovery of novel responsive promoters and their roles in fine-tuning metabolic networks. We also provide an outlook on the development trends in this field.

Keywords: Dynamic control; Metabolic engineering; Response element; Transcription regulation.

Graphical abstract

Fig. 1

Components and responses of a biosensor based on a responsive transcription factor and promoter system [22,27]. The ligand-binding domain of a transcription factor specifically detects input signals, resulting in a conformational change of the DNA-binding domain. The interaction between transcription factor (TF) and TF binding site (TFBS) regulates the transcription strength, which is reflected by output signals such as reporter proteins or enzymes in metabolic pathways.

Fig. 2

Light-responsive regulation system . After being activated by light, the photoreceptor protein usually undergoes homodimerization and interacts with upstream activation sequences (UAS) to initiate gene expression.

Fig. 3

Quorum-sensing (QS) dynamic control system mediated by α-pheromone . The concentration of α-pheromone secreted by cells increases as cell density increases. The binding of α-pheromone to the membrane receptor Ste2 activates the MAPK signaling pathway, leading to derepression of Ste12, which subsequently activates the transcription of the pheromone-responsive promoter P_FUS1.

Fig. 4

Dynamic control system via metabolite response. Biosensors are used to control key nodes in metabolic pathways by responding to metabolites changes. This enables the dynamic control of metabolic fluxes between cell growth phases and production phases.

Fig. 5

Dynamic regulation of metabolism by oxidation response elements. In response to oxidizing inducers or unfolded proteins, stress signals are transmitted from the cytoplasm or endoplasmic reticulum to nucleus, triggering gene expression.

Fig. 6

Discovery of stress-responsive promoters by omics-based tools.