Primary and Secondary Metabolic Effects of a Key Gene Deletion (Δ YPL062W ) in Metabolically Engineered Terpenoid-Producing Saccharomyces cerevisiae

Although computational and reverse metabolic engineering approaches often lead to improved gene deletion mutants for cell factory engineering, the systems level effects of such gene deletions on the production phenotypes have not been extensively studied. Understanding the genetic and molecular function of such gene alterations on production strains will minimize the risk inherent in the development of large-scale fermentation processes, which is a daunting challenge in the field of industrial biotechnology. Therefore, we established a detailed experimental and systems biology approach to uncover the molecular mechanisms ofYPL062W deletion inS. cerevisiae , which is shown to improve the production of all terpenoid classes. This study redefines the genetic function ofYPL062W , demonstrates a strong correlation betweenYPL062W and terpenoid production, and provides a useful modification for the creation of terpenoid production platform strains. Further, this study underscores the benefits of detailed and systematic characterization of the metabolic effects of genetic alterations on engineered biosynthetic factories.