(597g) Elucidating Core Design Principles to Engineer Nonconventional Yeasts As Novel Microbial Factories

Saccharomyces cerevisiae is far from being the only yeast of potential scientific and economic importance. Many of the 1800 other known yeast species have highly unusual metabolic, biosynthetic, physiological, and fermentative capacities. As outcomes of long-term natural evolution in particular environments, these high-performance characteristics are conferred by a network of genes via a hierarchy of regulations that are intrinsically complex, making the horizontal transfer of these functions into model hosts very challenging.

Three nonconventional yeast platforms will be discussed in this talk. First, we recently demonstrated Scheffersomyces stipitis as a better-suited platform to produce shikimate pathway derivatives, including various flavonoids and alkaloids, many of which have desired health-promoting activities. S. stipitis offers a higher availability of the rate-limiting precursor of the shikimate pathway due to its much more active pentose phosphate pathway. In the second platform, we are exploring Yarrowia lipolytica in producing long-chain wax esters as one of the major additives in the skin care products. Y. lipolytica, which is well known for its superior ability to accumulate triacylglycerol (TAG) under appropriate culturing condition and genetics combinations. Due to the biosynthesis of wax esters shares the same precursor with TAG biosynthesis, Y. lipolytica produced wax esters at a titer much higher than other reported hosts. Lastly, we will talk about how we engineer an acid tolerant strain Issatchenkia orientalis to produce itaconic acid, an important biopolymer precursor.

With these three exemplary projects, we will demonstrate how to overcome the technology hurdles that are commonly encountered when engineering nonconventional microorganisms. How to design systematic rules and enable generalizable platform technologies will be the focus of this presentation.