Abstract 2071 Heme biosynthesis facilitates branched chain amino acid catabolic flux and controls Ucp1 expression in brown adipose tissue through histone propionylation

Climate change, driven by increasing greenhouse gas emissions-particularly carbon dioxide (CO 2 )-remains a critical global challenge.The primary source of these emissions is the burning of fossil fuels for electricity, transportation, and heating.While efforts to reduce emissions are ongoing, a promising approach lies in using fast-fermenting, high-lipidproducing yeast strains to create renewable bioproducts from crop waste.The synthesis of these bioproducts relies on the essential coenzyme and 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 cellular damage.Under reductive stress, yeast cells lose their ability to produce bioproducts and eventually die.We hypothesize that decreased NAD+ recycling during cellular 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 NAD+ 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 through the salvage pathway significantly decreases.In R. toruloides IFO0880, the salvage pathway appears to remain functional, but increased NAD+ degradation still leads to a decline in NAD+ levels.Our findings suggest that enhancing salvage pathway activity in S. cerevisiae is essential to maintain consistent fermentation output and cellular homeostasis.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 cell survival and bioproduct yield.These advancements could play a significant role in reducing our reliance on fossil fuels, ultimately contributing to the fight against global warming and climate change.