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Biotechnol Bioeng. 2008 Aug 15;100(6):1039-49. doi: 10.1002/bit.21926.

Identification of optimal measurement sets for complete flux elucidation in metabolic flux analysis experiments.

Author information

1
Department of Chemical Engineering, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.

Abstract

Metabolic flux analysis (MFA) methods use external flux and isotopic measurements to quantify the magnitude of metabolic flows in metabolic networks. A key question in this analysis is choosing a set of measurements that is capable of yielding a unique flux distribution (identifiability). In this article, we introduce an optimization-based framework that uses incidence structure analysis to determine the smallest (or most cost-effective) set of measurements leading to complete flux elucidation. This approach relies on an integer linear programming formulation OptMeas that allows for the measurement of external fluxes and the complete (or partial) enumeration of the isotope forms of metabolites without requiring any of these to be chosen in advance. We subsequently query and refine the measurement sets suggested by OptMeas for identifiability and optimality. OptMeas is first tested on small to medium-size demonstration examples. It is subsequently applied to a large-scale E. coli isotopomer mapping model with more than 17,000 isotopomers. A number of additional measurements are identified leading to maximum flux elucidation in an amorphadiene producing E. coli strain.

PMID:
18553391
DOI:
10.1002/bit.21926
[Indexed for MEDLINE]

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