Origins of Cell-to-Cell Bioprocessing Diversity and Implications of the Extracellular Environment Revealed at the Single-Cell Level

• Main Authors: Vasdekis, A. E. (Author), Silverman, Andrew M. (Contributor), Stephanopoulos, Gregory (Contributor)
• Other Authors: Massachusetts Institute of Technology. Department of Chemical Engineering (Contributor)
• Format: Article
• Language: English
• Published: Nature Publishing Group, 2016-01-19T21:17:22Z.
• Subjects: Article
• Online Access: Get fulltext

Bioprocess limitations imposed by microbial cell-to-cell phenotypic diversity remain poorly understood. To address this, we investigated the origins of such culture diversity during lipid production and assessed the impact of the fermentation microenvironment. We measured the single-cell lipid production dynamics in a time-invariant microfluidic environment and discovered that production is not monotonic, but rather sporadic with time. To characterize this, we introduce bioprocessing noise and identify its epigenetic origins. We linked such intracellular production fluctuations with cell-to-cell productivity diversity in culture. This unmasked the phenotypic diversity amplification by the culture microenvironment, a critical parameter in strain engineering as well as metabolic disease treatment.
United States. Dept. of Energy (Grant SC 0008744)
National Institute of General Medical Sciences (U.S.) (Institutional Development Award P20 GM103408)
Pacific Northwest National Laboratory (U.S.) (Linus Pauling Fellowship PN12005/2406)