4.7 Review

Overcoming Challenges in Expressing Iron-Sulfur Enzymes in Yeast

Journal

TRENDS IN BIOTECHNOLOGY
Volume 39, Issue 7, Pages 665-677

Publisher

CELL PRESS
DOI: 10.1016/j.tibtech.2020.11.005

Keywords

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Funding

  1. NSERC Industrial Biocatalysis Network (IBN) from the Natural Sciences and Engineering Research Council (NSERC)
  2. grant 'Biochemicals from Cellulosic Biomass (BioCeB)' from the Ontario Research Fund (Research Excellence)
  3. grant 'Genomics Applied Partnership Program (GAPP)' from Genome Canada

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This review discusses the challenge of high-level expression of bacterial iron-sulfur enzymes in yeast, pointing out the issue of intermediate accumulation. Possible explanations are proposed, genetic interventions are discussed, and future directions for improving yeast hosts for high iron-sulfur enzyme expression are suggested.
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.

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