Genomic Science Program
U.S. Department of Energy | Office of Science | Biological and Environmental Research Program

Lipid Membrane Biology of Microbial Cell Factories During Microaerobic Fermentation

Authors:

Itay Budin* (ibudin@ucsd.ed), Kailash Venkatraman, Nicolas Frédéric Lipp, Israel Juarez-Contreras

Institutions:

University of California–San Diego

Goals

The goal of this Early Career Program project is to engineer the structure and properties of cell membranes to improve the performance of industrially relevant microbes. The project’s first objective is to enhance the rate and efficiency of the respiratory metabolism by engineering the organization of the electron transport chain. Engineering efforts will define the limits of respiratory metabolism and seek to increase the production of energy-intensive next-generation biofuels. The second objective is to apply the emerging biochemistry of intracellular lipid trafficking pathways to develop new transporters for the capture of valuable biochemicals produced by the engineered yeast.

Abstract

The project will present advancements in three areas of lipid membrane biology relevant for the performance of yeast microbial cell factories. In the first direction, the team has elucidated key factors that allow for mitochondrial function in fermentation conditions that are characterized by low oxygen availability. Paradoxically, mitochondria proliferate under these conditions, and the inner mitochondrial membrane increases its surface area and complexity. Researchers have found that synthesis and remodeling of the tetra-acyl lipid cardiolipin is essential under microaerobic fermentation due to lipidomic changes resulting from the loss of oxygen-dependent desaturase activity. In the second direction, researchers have characterized a putative lipid transfer protein (LTP) that is predicted to bind squalene, a biolubricant and intermediate in ergosterol biosynthesis. Researchers have found that loss of this LTP, Sfh2, results in accumulation of squalene under microaerobic conditions. The team is currently testing if this LTP traffics squalene from its site of synthesis in the endoplasmic reticulum to storage sites in lipid droplets in vivo. The project is also testing its in vitro activity and proposes that it could be harnessed to better extract squalene from cell factories. In the third direction, researchers have engineered sterol metabolism in yeast to develop cells that better tolerate high temperature and low oxygen fermentations. The project envisions these strains as allowing for new bioproduction capacities outside of standard conditions.

References

Venkatraman, K., et al. 2023. “Cristae Formation Is a Mechanical Buckling Event Controlled by the Inner Mitochondrial Membrane Lipidome,” The EMBO Journal. DOI:10.15252/embj.2023114054.

Funding Information

This research is supported by the DOE Office of Science, BER program, grant no. DE-SC0022954.