Synthetic sensing systems in Saccharomyces cerevisiae

Abstract

The yeast Saccharomyces cerevisiae is a major chemical production platform in the biotechnological industry. It is also increasingly being used as a whole cell biosensor. One method of developing such whole cell biosensors in yeast is by exploiting its mating pathway, which is normally induced by secreted pheromones leading to downstream expression of various genes. Functional expression of different recognition elements or receptors and their coupling to the yeast mating pathway can enable sensing of a variety of ligands. In this work, we have engineered a yeast strain to functionally express a heterologous human olfactory receptor gene which can be coupled to the pheromone signaling pathway, allowing yeast to detect medium chain length fatty acids, alcohols and aldehydes for the first time. Functionally expressing heterologous olfactory receptors in yeast is a challenging task because no definitive method exists on how to express such receptors on the yeast cell surface and couple them to the downstream signaling pathway. We explore in this work how the yeast cell can selectively respond to two activating ligands via two different receptors. We also demonstrate in this work that a synthetic transcription factor can substitute for the native transcription factor in the yeast mating pathway. We believe our biosensor will not only have various uses as a versatile sensor but also aid in the design of synthetic genetic circuits.