title: Origins of Cell-to-Cell Bioprocessing Diversity and Implications of the Extracellular Environment Revealed at the Single-Cell Level.
abstract: 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.
authors.affiliation: Department of Physics, University of Idaho, Moscow, ID, 83844, USA.|Environmental and Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, WA, 99354, USA.
authors.forename: A E
authors.initials: AE
authors.lastname: Vasdekis
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Silverman
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: G
authors.initials: G
authors.lastname: Stephanopoulos
mesh_terms: D019149:Bioreactors; D005285:Fermentation; D005658:Fungi; D050356:Lipid Metabolism; D008055:Lipids / Q000096:biosynthesis*; D010641:Phenotype
chemical_list: D008055:Lipids