Innovating a Nonconventional Yeast Platform for Producing Shikimate as the Building Block of High-Value Aromatics

The shikimate pathway serves an essential role in many organisms. Not only are the three aromatic amino acids synthesized through this pathway, but many secondary metabolites also derive from it. Decades of effort have been invested into engineering Saccharomyces cerevisiae to produce shikimate and its derivatives. In addition to the ability to express cytochrome P450, S. cerevisiae is generally recognized as safe for producing compounds with nutraceutical and pharmaceutical applications. However, the intrinsically complicated regulations involved in central metabolism and the low precursor availability in S. cerevisiae has limited production levels. Here we report the development of a new platform based on Scheffersomyces stipitis, whose superior xylose utilization efficiency makes it particularly suited to produce the shikimate group of compounds. Shikimate was produced at 3.11 g/L, representing the highest level among shikimate pathway products in yeasts. Our work represents a new exploration toward expanding the current collection of microbial factories.