Construction of multidrug-sensitive yeast with high sporulation efficiency

Area of Science:

• Chemical genetics
• Molecular biology
• Yeast genetics

Background:

• Budding yeast is a valuable model organism for chemical genetics applications like screening and target identification.
• High-level drug resistance in yeast strains complicates the analysis of compounds and limits their utility in research.
• Existing yeast strains possess efflux pumps and transcription factors that confer resistance to various compounds.

Purpose of the Study:

• To construct a novel budding yeast strain with enhanced sensitivity to chemical compounds.
• To facilitate improved chemical genetics screening, target identification, and compound verification.
• To address the limitations posed by drug resistance in traditional yeast models.

Main Methods:

• Construction of the 12geneΔ0HSR yeast strain by deleting genes encoding eight plasma membrane efflux pumps and four transcription factors.
• Introduction of the RME1(ins-308A) mutation into the yeast strain.
• Assessment of the strain's transformation, mating, and sporulation efficiencies, alongside its compound hypersensitivity.

Main Results:

• The 12geneΔ0HSR strain exhibits hypersensitivity to several compounds, indicating reduced drug resistance.
• The strain maintains essential genetic analysis capabilities, including transformation, mating, and sporulation efficiency.
• The engineered strain serves as a potent tool for chemical biology applications.

Conclusions:

• The 12geneΔ0HSR strain is a valuable tool for chemical biology, overcoming the limitations of drug resistance in budding yeast.
• This strain significantly improves the efficacy of chemical screening, target identification, and verification of bioactive compounds.
• The development of 12geneΔ0HSR advances the application of yeast models in drug discovery and chemical genetics research.