The RAVEN toolbox and its use for generating a genome-scale metabolic model for Penicillium chrysogenum

PLoS Comput Biol. 2013;9(3):e1002980. doi: 10.1371/journal.pcbi.1002980. Epub 2013 Mar 21.

Abstract

We present the RAVEN (Reconstruction, Analysis and Visualization of Metabolic Networks) Toolbox: a software suite that allows for semi-automated reconstruction of genome-scale models. It makes use of published models and/or the KEGG database, coupled with extensive gap-filling and quality control features. The software suite also contains methods for visualizing simulation results and omics data, as well as a range of methods for performing simulations and analyzing the results. The software is a useful tool for system-wide data analysis in a metabolic context and for streamlined reconstruction of metabolic networks based on protein homology. The RAVEN Toolbox workflow was applied in order to reconstruct a genome-scale metabolic model for the important microbial cell factory Penicillium chrysogenum Wisconsin54-1255. The model was validated in a bibliomic study of in total 440 references, and it comprises 1471 unique biochemical reactions and 1006 ORFs. It was then used to study the roles of ATP and NADPH in the biosynthesis of penicillin, and to identify potential metabolic engineering targets for maximization of penicillin production.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Bioengineering
  • Computational Biology / methods
  • Databases, Genetic
  • Genome, Bacterial
  • Metabolic Networks and Pathways
  • Models, Biological*
  • NADP / metabolism
  • Penicillins / metabolism
  • Penicillium chrysogenum / genetics*
  • Penicillium chrysogenum / metabolism*
  • Software

Substances

  • Penicillins
  • NADP
  • Adenosine Triphosphate

Grant support

This project has been financed by European Research Council (Grant 247013), the EU-funded project SYSINBIO and Sandoz. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.