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

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 produ...

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Bibliographic Details
Published in:Scientific reports 2015-12, Vol.5 (1), p.17689-17689, Article 17689
Main Authors: Vasdekis, A. E., Silverman, A. M., Stephanopoulos, G.
Format: Article
Language:English
Subjects:
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BASIC BIOLOGICAL SCIENCES
biophysical methods
Bioreactors
Biosynthesis
Cell culture
Enzymes
Epigenetics
Fermentation
Fungi
Gene expression
Humanities and Social Sciences
Investigations
Laboratories
Lipid Metabolism
Lipids
Lipids - biosynthesis
Medical treatment
Metabolic disorders
Metabolic engineering
Metabolism
Metabolites
Microfluidics
multidisciplinary
Phenotype
Productivity
Science
Standard deviation
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep17689