Exploiting Bioprocessing Fluctuations to Elicit the Mechanistics of De Novo Lipogenesis in Yarrowia lipolytica
Name
Vasdekis-2017-Exploiting Bioprocessing Fluctua.pdf
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1.66 MB
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Author(s)
Vasdekis, Andreas E.
Silverman, Andrew Michael
Stephanopoulos, Gregory
Date Issued
January 2017
Journal
PLoS ONE
Publisher
Public Library of Science
Citation
Vasdekis, Andreas E.; Silverman, Andrew M. and Stephanopoulos, Gregory. “Exploiting Bioprocessing Fluctuations to Elicit the Mechanistics of De Novo Lipogenesis in Yarrowia Lipolytica.” Edited by Thierry Chardot. PLOS ONE 12, no. 1 (January 2017): e0168889 © 2017 Vasdekis et al
Version
Final published version
Abstract
Despite substantial achievements in elucidating the metabolic pathways of lipogenesis, a mechanistic representation of lipid accumulation and degradation has not been fully attained to-date. Recent evidence suggests that lipid accumulation can occur through increases of either the cytosolic copy-number of lipid droplets (LDs), or the LDs size. However, the prevailing phenotype, or how such mechanisms pertain to lipid degradation remain poorly understood. To address this shortcoming, we employed the–recently discovered–innate bioprocessing fluctuations in Yarrowia lipolytica, and performed single-cell fluctuation analysis using optical microscopy and microfluidics that generate a quasi-time invariant microenvironment. We report that lipid accumulation at early stationary phase in rich medium is substantially more likely to occur through variations in the LDs copy-number, rather than the LDs size. Critically, these mechanistics are also preserved during lipid degradation, as well as upon exposure to a protein translation inhibitor. The latter condition additionally induced a lipid accumulation phase, accompanied by the downregulation of lipid catabolism. Our results enable an in-depth mechanistic understanding of lipid biogenesis, and expand longitudinal single-cell fluctuation analyses from gene regulation to metabolism.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
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Creative Commons Attribution 4.0 International License
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DOI of Published Version
http://dx.doi.org/10.1371/journal.pone.0168889
