Optimizing Microbial Bioproduction of Fuels

Identifying factors that contribute to cell-to-cell variability in lipid production.

The Science

Microbial strains engineered to produce a large amount of lipids hold tremendous promise for the production of biofuels and chemicals. A recent study shed light on underlying causes of microbial cell-to-cell variability in lipid production.

The Impact

The findings revealed that conditions within cells and in the surrounding environment interact to contribute to variability in lipid production. The new insights could lead to strategies that optimize the use of engineered microbial strains for the production of important biofuels and chemicals.


The microbial production of biofuels and chemicals often does not reach the theoretical maximum yield, even for engineered strains, thereby limiting the reliability of large-scale bioprocessing. To understand the limitations, scientists have started to investigate the reasons for phenotypic diversity of cells within a culture. A team of scientists from the University of Idaho, Environmental Molecular Sciences Laboratory (EMSL), and Massachusetts Institute of Technology used advanced microfluidics combined with Epifluorescent and Raman microscopy at EMSL to study differences in the ability of individual cells of low-yield and high-yield strains of the fungus Yarrowia lipolytica to produce lipids. The researchers found lipid production fluctuated sporadically with time in both strains. The researchers labeled this newly discovered phenomenon “bioprocessing noise.” Furthermore, the high-yield fungal strain showed reduced bioprocessing noise in lipid production than the low-yield fungal strain. This finding indicates differences in the activity of key metabolic genes that contribute to bioprocessing noise and thus cellular diversity in lipid production. Moreover, this variability was amplified by environmental factors such as chemical gradients of nutrients or waste products surrounding cells. Taken together, these findings show extracellular and intracellular fluctuations interact to place an upper limit on the reliability of lipid production and total yield of lipids. This research could pave the way for new strategies to improve the reliability and efficiency of using engineered microbial strains for the production of lipids that could then be converted to valuable biofuels or chemicals.

Principal Investigator(s)

Andreas Vasdekis
University of Idaho

Gregory Stephanopoulos
Massachusetts Institute of Technology

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This work was supported by the U.S. Department of Energy’s Office of Science, Office of Biological and Environmental Research, including support of EMSL, a DOE Office of Science user facility; National Institute of General Medical Sciences of the National Institutes of Health; and a Linus Pauling Fellowship from Pacific Northwest National Laboratory.


Vasdekis, A. E., A. M. Silverman, and G. Stephanopoulos. 2015. “Origins of Cell-to-Cell Bioprocessing Diversity and Implications of the Extracellular Environment Revealed at the Single-Cell Level,” Nature Scientific Reports 5(17689), DOI: 10.1038/srep17689.