Synthetic Biology for Engineering Acetyl Coenzyme A Metabolism in Yeast

ABSTRACT The yeast Saccharomyces cerevisiae is a widely used cell factory for the production of fuels, chemicals, and pharma-ceuticals. The use of this cell factory for cost-efficient production of novel fuels and chemicals requires high yields and low by-product production. Many industrially interesting chemicals are biosynthesized from acetyl coenzyme A (acetyl-CoA), which serves as a central precursor metabolite in yeast. To ensure high yields in production of these chemicals, it is necessary to engi-neer the central carbonmetabolism so that ethanol production is minimized (or eliminated) and acetyl-CoA can be formed from glucose in high yield. Here the perspective of generating yeast platform strains that have such properties is discussed in the con-text of a major breakthrough with expression of a functional pyruvate dehydrogenase complex in the cytosol. There aremanyprospects for usingmicroorganisms for sustain-able production of fuels and chemicals, and even though the 2010 market for renewable chemicals was only about 1 % of the total chemical market, i.e., about $30 billion out of a total of $3,000 billion, it has the potential to grow to $80 billion by 2020. To support this expansion in production, it is necessary to develop efficient cell factories throughmetabolic engineering (1), and here the yeast Saccharomyces cerevisiae is among the preferred cell fac-tories in industry (2). In order for a novel bioprocess to be eco