Enhancing/Elucidating NAD+ Homeostasis in Yeast to Improve Biofuel Production
Research Poster Health & Life Sciences 2025 Graduate ExhibitionPresentation by Alexandria Murphy
Exhibition Number 204
Abstract
Climate change, driven by greenhouse gas emissions—carbon dioxide (CO)—remains a critical global challenge. The primary source of these emissions is the burning of fossil fuels. While efforts to reduce emissions are ongoing, a promising approach lies in using fast-fermenting, high-lipid-producing yeast strains to create renewable bioproducts from crop waste. The synthesis of these bioproducts relies on the essential cofactor NAD+, making it crucial to understand NAD+ synthesis and degradation. Previous studies have shown that as yeast cells age, their NAD+ levels decline while NADH levels rise, leading to redox stress and damage. Under reductive stress, yeast cells lose their ability to produce and die. We hypothesize that decreased NAD+ recycling during aging reduces the output of desired bioproducts. To investigate this, we designed experiments using stable isotope-labeled NAD+ precursors to track the entire NAD metabolome and understand dynamics. We tested this approach under basal conditions in Saccharomyces cerevisiae, a fermenting yeast, and Rhodotorula toruloides IFO0880, a high-lipid-producing yeast. Preliminary results show that in S. cerevisiae, NAD+ degradation increases over time, while NAD+ recycling significantly decreases. In R. toruloides IFO0880, the salvage pathway appears to remain functional, but increased NAD+ degradation still leads to a decline. Our findings suggest that enhancing salvage pathway activity in S. cerevisiae is essential to maintain consistent fermentation. Additionally, identifying and inhibiting the enzymes responsible for rapid NAD+ degradation in R. toruloides IFO0880 could boost lipid production. By addressing these vulnerabilities in yeast metabolism, targeted interventions can improve survival and bioproduct yield.
Importance
Climate change is a global crisis. As we are in desperate need to replace fossil fuels in our everyday lives, using renewable energy is a necessity. Yeast is a cost effective and efficient tool to use when manufacturing bioproducts. To use this tool on a global scale we must understand how yeast metabolism works, and where the vulnerabilities lie.