Overcoming Challenges in Expressing Iron-Sulfur Enzymes in Yeast

Iron-sulfur clusters are metal cofactors that are present in all domains of life. Many enzymes that require these cofactors have biotechnological importance, because they can be used to uncover catabolic routes to new sugar substrates or can be a critical part of pathways to produce chemicals and biofuels. However, the expression of these iron-sulfur enzymes of bacterial origin in yeast at high levels is a significant bottleneck. Intermediates upstream of the enzyme accumulate, because the activity of these enzymes is either low or completely absent. In this review, we examine possible explanations for this limitation, discuss potential genetic interventions in the yeast host that can increase iron-sulfur enzyme activity, and suggest future directions for creating more efficient yeast hosts capable of high iron-sulfur enzyme expression.