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Optimizing Microbial Bioproduction of Fuels

Identifying factors that contribute to cell-to-cell variability in lipid production A team of scientists investigated origins of culture diversity during lipid production and assessed the fermentation microenvironment at the single-cell level for better understanding of bioprocess limitations.

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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 reveal 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 limitations, scientists have started to investigate reasons for phenotypic diversity of cells within a culture. A team of scientists from the University of Idaho; EMSL, the Environmental Molecular Sciences Laboratory; and the Massachusetts Institute of Technology has 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 authors 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 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, the findings show extracellular and intracellular fluctuations interact to place an upper limit on the reliability of lipid production and the 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.


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; the National Institute of General Medical Sciences of the National Institutes of Health; and a Linus Pauling Fellowship from the Pacific Northwest National Laboratory.


A.E. Vasdekis, A.M. Silverman and G. Stephanopoulos, “Origins of cell-to-cell bioprocessing diversity and implications of the extracellular environment revealed at the single-cell level.” Nature Scientific Reports 5,17689 (2015). [DOI: 10.1038/srep17689]