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Cited by 255

The DOI matches its Crossref record; 21 of the 21 references it cites were found in a registry or an index.

An elementary metabolite unit (EMU) based method of isotopically nonstationary flux analysis

Young, Jamey D., Walther, Jason L., Antoniewicz, Maciek R., Yoo, Hyuntae, Stephanopoulos, Gregory·2008·Biotechnology and Bioengineering

Abstract

Nonstationary metabolic flux analysis (NMFA) is at present a very computationally intensive exercise, especially for large reaction networks. We applied elementary metabolite unit (EMU) theory to NMFA, dramatically reducing computational difficulty. We also introduced block decoupling, a new method that systematically and comprehensively divides EMU systems of equations into smaller subproblems to further reduce computational difficulty. These improvements led to a 5000‐fold reduction in simulation times, enabling an entirely new and more complicated set of problems to be analyzed with NMFA. We simulated a series of nonstationary and stationary GC/MS measurements for a large E. coli network that was then used to estimate parameters and their associated confidence intervals. We found that fluxes could be successfully estimated using only nonstationary labeling data and external flux measurements. Addition of near‐stationary and stationary time points increased the precision of most parameters. Contrary to prior reports, the precision of nonstationary estimates proved to be comparable to the precision of estimates based solely on stationary data. Finally, we applied EMU‐based NMFA to experimental nonstationary measurements taken from brown adipocytes and successfully estimated fluxes and some metabolite concentrations. By using NFMA instead of traditional MFA, the experiment required only 6 h instead of 50 (the time necessary for most metabolite labeling to reach 99% of isotopic steady state). Biotechnol. Bioeng. 2008;99: 686–699. © 2007 Wiley Periodicals, Inc.

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Crossref · 10.1002/bit.21632

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Metadata

Authors
Young, J. D., Walther, J. L., Antoniewicz, M. R., Yoo, H., & Stephanopoulos, G.
Venue
Biotechnology and Bioengineering
Publisher
Wiley
Published
2007-09-04
Volume
99
Issue
3
Pages
686-699
ISSN
  • 0006-3592 (ISSN-L)
  • 1097-0290
OpenAlex
W2148497594
Cited by
255
References
21
FWCI
3.83
Type
journal article
Language
en
Open access
closed

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