A toolkit for precise, multigene control in Saccharomyces cerevisiae

Systems that allow researchers to precisely control the expression of
genes are fundamental to biological research, biotechnology, and synthetic
biology. However, few inducible gene expression systems exist that can
enable simultaneous, multi-gene control in the important model organism
and chassis, Saccharomyces cerevisiae. Here, we repurposed ligand binding
domains (LBDs) from mammalian Type I nuclear receptors to establish a
family of up to five orthogonal synthetic gene expression systems in
yeast. Our systems enable tight, independent, multi-gene control through
the addition of inert hormones, and are capable of driving robust gene
expression outputs. As a proof-of-principle, we placed expression of four
enzymes from the violacein biosynthetic pathway under independent
expression control to selectively route pathway flux. Our results
establish a modular, versatile, and potentially expandable toolkit for
multidimensional control of gene expression in yeast that can be used to
construct and control naturally-occurring and synthetic gene networks.