The wide-ranging phenotypes of ergosterol biosynthesis mutants, and implications for microbial cell factories.

ABSTRACT

Yeast strains have been used extensively as robust microbial cell factories for the production of bulk and fine chemicals, including biofuels (bioethanol), complex pharmaceuticals (antimalarial drug artemisinin and opioid pain killers), flavours, and fragrances (vanillin, nootkatone, and resveratrol). In many cases, it is of benefit to suppress or modify ergosterol biosynthesis during strain engineering, for example, to increase thermotolerance or to increase metabolic flux through an alternate pathway. However, the impact of modifying ergosterol biosynthesis on engineered strains is discussed sparsely in literature, and little attention has been paid to the implications of these modifications on the general health and well-being of yeast. Importantly, yeast with modified sterol content exhibit a wide range of phenotypes, including altered organization and dynamics of plasma membrane, altered susceptibility to chemical treatment, increased tolerance to high temperatures, and reduced tolerance to other stresses such as high ethanol, salt, and solute concentrations. Here, we review the wide-ranging phenotypes of viable Saccharomyces cerevisiae strains with altered sterol content and discuss the implications of these for yeast as microbial cell factories.