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Carbon Source Drives Phenotypic Behavior in Lipomyces starkeyi

The Science 

Yeasts play important roles in everyday life. They’re used to bake bread, ferment alcohol, and produce antibiotics and a variety of pharmaceuticals and chemicals. Currently, deep knowledge has been attained for only a couple types of yeasts. This limits scientific ability to leverage new yeasts in biotechnology applications. Researchers at Pacific Northwest National Laboratory (PNNL) studied Lipomyces starkeyi, a yeast that has limited coverage in existing literature but potential for fuels and chemical productionThey characterized how Lipomyces functions, evaluated its stress tolerance and redox balancing to different carbon sources, and uncovered regulatory networks, all of which is useful knowledge for engineering the yeast for beneficial purposes such as producing organic acids and lipids for industrial uses.

The Impact 

Researchers used advanced measurement tools to evaluate how L. starkeyi grew on industrial carbon sources, enabling the team to uncover how the yeast functions and regulates itself at the molecular level. This data is interpretable by AI and machine learning to help identify control points that can be manipulated to improve process performance, such as having the yeast make more of a fuel, chemical, or other product. Furthermore, their research uncovered how the choice of carbon source influences stress tolerance and redox balance, which can help provide resilience against scale-up challenges. Overall, this work deepens the knowledge of Lipomyces to enable the development of new engineering strategies to produce valuable commodity chemicals.

Summary 

Lipomyces is a genus of oleaginous yeasts with potential to contribute to reliable biomanufacturing supply chains. However, progress in advanced strain design and engineering is constrained by a lack of understanding of the underlying molecular drivers of Lipomyces phenotypes. To address this gap, researchers collected a suite of multi-omics data to dissect how carbon source availability reshapes the metabolic network, lipid allocation, and regulatory architecture of L. starkeyi. They studied microbial response to glucose, xylose, and glycerol as carbon sources. They found that glucose promotes biosynthetic and proliferative processes supported by abundant energy and carbon intermediates, xylose enhances redox-balancing mechanisms centered on the pentose phosphate pathway, and glycerol activates respiratory metabolism, β-oxidation, and the glyoxylate cycle. They found that glycerol-driven growth favors regulatory programs that integrate stress tolerance, redox balance, and lipid-associated metabolism, whereas xylose growth activates compensatory transcriptional responses aimed at maintaining mitochondrial function. Nitrogen limitation affects the strength of these responses but does not alter their direction, reinforcing that the carbon source is the dominant driver of regulatory architecture. Taken together, this data enhances the understanding of the molecular rearrangements of Lipomyces and provides a foundation for further development of predictive phenotypic tools in this genus.

Contact 

Jeffrey Czajka, Pacific Northwest National Laboratory, jeffrey.czajka@pnnl.gov

Lummy Monteiro, Pacific Northwest National Laboratory, lummy.monteiro@pnnl.gov

Funding 

This work was supported by the PNNL Laboratory Directed Research and Development program and is a contribution of the Predictive Phenomics Initiative. PNNL is operated by Battelle Memorial Institute for the Department of Energy under contract no. DE-AC05–76RL01830.

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