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Title: Eliciting the impacts of cellular noise on metabolic trade-offs by quantitative mass imaging

Abstract

Metabolic trade-offs between growth and productivity are key constraints in metabolic engineering and adaptive evolution; however, how cellular noise impacts these trade offs and drives the emergence of subpopulations with distinct resource allocation strategies, remains largely unknown. Here, we introduce a single-cell strategy for quantifying the trade-offs between triacylglycerol production and growth in the oleaginous microorganism Yarrowia lipolytica. The strategy relies on high-throughput quantitative-phase imaging and, enabled by nanoscale secondary ion mass spectrometry analyses and dedicated image processing, allows us to image how resources are partitioned between growth and productivity. Enhanced precision over population-averaging biotechnologies and conventional microscopy demonstrates how cellular noise impacts growth and productivity differently. As such, subpopulations with distinct metabolic trade-offs emerge, with notable impacts on strain performance and robustness. By quantifying autophagic catabolic fluxes under nutrient-limiting conditions, we discover an underlying cell-to-cell heterogeneity in protein and fatty-acid recycling, unmasking a potential bet-hedging survival strategy under starvation.

Authors:
 [1];  [1];  [2];  [1];  [1];  [3];  [3];  [2]
  1. Univ. of Idaho, Moscow, ID (United States)
  2. Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States)
  3. Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1507525
Report Number(s):
PNNL-SA-141117
Journal ID: ISSN 2041-1723
Grant/Contract Number:  
AC05-76RL01830; SC0019249; P20GM104420; SC0008744; 49084
Resource Type:
Accepted Manuscript
Journal Name:
Nature Communications
Additional Journal Information:
Journal Volume: 10; Journal Issue: 1; Journal ID: ISSN 2041-1723
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; lipids; Yarrowia lipolytica; triacylglycerol

Citation Formats

Vasdekis, Andreas E., Alanazi, H., Silverman, Andrew M., Williams, C. J., Canul, Amrah J., Cliff, John B., Dohnalkova, Alice C., and Stephanopoulos, Gregory. Eliciting the impacts of cellular noise on metabolic trade-offs by quantitative mass imaging. United States: N. p., 2019. Web. doi:10.1038/s41467-019-08717-w.
Vasdekis, Andreas E., Alanazi, H., Silverman, Andrew M., Williams, C. J., Canul, Amrah J., Cliff, John B., Dohnalkova, Alice C., & Stephanopoulos, Gregory. Eliciting the impacts of cellular noise on metabolic trade-offs by quantitative mass imaging. United States. doi:10.1038/s41467-019-08717-w.
Vasdekis, Andreas E., Alanazi, H., Silverman, Andrew M., Williams, C. J., Canul, Amrah J., Cliff, John B., Dohnalkova, Alice C., and Stephanopoulos, Gregory. Tue . "Eliciting the impacts of cellular noise on metabolic trade-offs by quantitative mass imaging". United States. doi:10.1038/s41467-019-08717-w. https://www.osti.gov/servlets/purl/1507525.
@article{osti_1507525,
title = {Eliciting the impacts of cellular noise on metabolic trade-offs by quantitative mass imaging},
author = {Vasdekis, Andreas E. and Alanazi, H. and Silverman, Andrew M. and Williams, C. J. and Canul, Amrah J. and Cliff, John B. and Dohnalkova, Alice C. and Stephanopoulos, Gregory},
abstractNote = {Metabolic trade-offs between growth and productivity are key constraints in metabolic engineering and adaptive evolution; however, how cellular noise impacts these trade offs and drives the emergence of subpopulations with distinct resource allocation strategies, remains largely unknown. Here, we introduce a single-cell strategy for quantifying the trade-offs between triacylglycerol production and growth in the oleaginous microorganism Yarrowia lipolytica. The strategy relies on high-throughput quantitative-phase imaging and, enabled by nanoscale secondary ion mass spectrometry analyses and dedicated image processing, allows us to image how resources are partitioned between growth and productivity. Enhanced precision over population-averaging biotechnologies and conventional microscopy demonstrates how cellular noise impacts growth and productivity differently. As such, subpopulations with distinct metabolic trade-offs emerge, with notable impacts on strain performance and robustness. By quantifying autophagic catabolic fluxes under nutrient-limiting conditions, we discover an underlying cell-to-cell heterogeneity in protein and fatty-acid recycling, unmasking a potential bet-hedging survival strategy under starvation.},
doi = {10.1038/s41467-019-08717-w},
journal = {Nature Communications},
number = 1,
volume = 10,
place = {United States},
year = {2019},
month = {2}
}

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