Computer-Driven Construction of a Saccharomyces cerevisiae Aromatase Inhibitor Screening Platform

Saccharomyces cerevisiae is a cost-effective eukaryotic chassis for hosting synthetic circuits that include heterologously expressed proteins. The budding yeast has been extensively used across multiple biotechnological sectors, including environmental applications and pharmaceutical production. Here, we describe a rational workflow for the design and implementation of an S. cerevisiae-based screening platform for aromatase inhibitors. The workflow is organized into three main components: (1) the design and construction of an efficient β-estradiol biosensor; (2) the engineering of a yeast expression system for human aromatase (CYP19A1) and cytochrome P450 reductase; and (3) a screening method for identifying aromatase inhibitors and determining the IC₅₀ values of the most effective compounds. The aromatase inhibitors identified using this platform represent potential therapeutic candidates for a specific subtype of breast cancer.