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

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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.I would like to thank the Center for Advanced Bioenergy and Bioproduct Innovation (CABBI) for funding my work on this project.

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