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Title: EMUlator: An Elementary Metabolite Unit (EMU) Based Isotope Simulator Enabled by Adjacency Matrix

Journal Article · · Frontiers in Microbiology
 [1];  [2];  [1];  [1];  [1];  [1]
  1. National Renewable Energy Laboratory (NREL), Golden, CO (United States)
  2. Inst. of Nuclear Energy Research, Taoyuan (Taiwan)

Stable isotope based metabolic flux analysis is currently the unique methodology that allows the experimental study of the integrated responses of metabolic networks. This method primarily relies on isotope labeling and modeling, which could be a challenge in both experimental and computational biology. Specifically, the algorithm implementation for isotope simulation is a critical step, limiting extensive usage of this powerful approach. In this work, we introduce EMUlator a Python-based isotope simulator which is developed on Elementary Metabolite Unit (EMU) algorithm, an efficient and powerful algorithm for isotope modeling. We propose a novel adjacency matrix method to implement EMU modeling and exemplify it stepwise. This method is intuitively straightforward and can be conveniently mastered for various customized purposes. We apply this arithmetic pipeline to understand the phosphoketolase flux in the metabolic network of an industrial microbe Clostridium acetobutylicum. The resulting design enables a high-throughput and non-invasive approach for estimating phosphoketolase flux in vivo. Our computational insights allow the systematic design and prediction of isotope-based metabolic models and yield a comprehensive understanding of their limitations and potentials.

Research Organization:
National Renewable Energy Laboratory (NREL), Golden, CO (United States)
Sponsoring Organization:
USDOE National Renewable Energy Laboratory (NREL), Laboratory Directed Research and Development (LDRD) Program; USDOE Office of Energy Efficiency and Renewable Energy (EERE), Office of Sustainable Transportation and Fuels. Bioenergy Technologies Office (BETO)
Grant/Contract Number:
AC36-08GO28308
OSTI ID:
1514834
Report Number(s):
NREL/JA-2700-73924
Journal Information:
Frontiers in Microbiology, Vol. 10; ISSN 1664-302X
Publisher:
Frontiers Research FoundationCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 3 works
Citation information provided by
Web of Science

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An elementary metabolite unit (EMU) based method of isotopically nonstationary flux analysis journal February 2008
Evaluation of 13C isotopic tracers for metabolic flux analysis in mammalian cells journal November 2009
Transcriptional analysis of catabolite repression in Clostridium acetobutylicum growing on mixtures of d-glucose and d-xylose journal November 2010
Determination of confidence intervals of metabolic fluxes estimated from stable isotope measurements journal July 2006
Parallel labeling experiments validate Clostridium acetobutylicum metabolic network model for 13C metabolic flux analysis journal November 2014
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Metabolic networks in motion: 13 C‐based flux analysis journal January 2006
Synthetic non-oxidative glycolysis enables complete carbon conservation journal September 2013
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Genome-Scale Fluxome of Synechococcus elongatus UTEX 2973 Using Transient 13 C-Labeling Data journal December 2018
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Figures / Tables (8)