Format

Send to

Choose Destination
Biotechnol J. 2016 May;11(5):648-61. doi: 10.1002/biot.201500267. Epub 2016 Mar 9.

MapMaker and PathTracer for tracking carbon in genome-scale metabolic models.

Author information

1
Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, Wisconsin, USA.
2
Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, Wisconsin, USA. reed@engr.wisc.edu.

Abstract

Constraint-based reconstruction and analysis (COBRA) modeling results can be difficult to interpret given the large numbers of reactions in genome-scale models. While paths in metabolic networks can be found, existing methods are not easily combined with constraint-based approaches. To address this limitation, two tools (MapMaker and PathTracer) were developed to find paths (including cycles) between metabolites, where each step transfers carbon from reactant to product. MapMaker predicts carbon transfer maps (CTMs) between metabolites using only information on molecular formulae and reaction stoichiometry, effectively determining which reactants and products share carbon atoms. MapMaker correctly assigned CTMs for over 97% of the 2,251 reactions in an Escherichia coli metabolic model (iJO1366). Using CTMs as inputs, PathTracer finds paths between two metabolites. PathTracer was applied to iJO1366 to investigate the importance of using CTMs and COBRA constraints when enumerating paths, to find active and high flux paths in flux balance analysis (FBA) solutions, to identify paths for putrescine utilization, and to elucidate a potential CO2 fixation pathway in E. coli. These results illustrate how MapMaker and PathTracer can be used in combination with constraint-based models to identify feasible, active, and high flux paths between metabolites.

KEYWORDS:

Carbon flux; Carbon transfer maps (CTMs); Flux balance analysis (FBA); Metabolic pathway; Parsimonious FBA

PMID:
26771089
PMCID:
PMC4921238
DOI:
10.1002/biot.201500267
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center