RAVEN 2.0: A versatile toolbox for metabolic network reconstruction and a case study on Streptomyces coelicolor.

Wang H, Marcišauskas S, Sánchez BJ, Domenzain I, Hermansson D, Agren R, Nielsen J, Kerkhoven EJ

PLoS Comput. Biol. 14 (10) e1006541 [2018-10-00; online 2018-10-18]

RAVEN is a commonly used MATLAB toolbox for genome-scale metabolic model (GEM) reconstruction, curation and constraint-based modelling and simulation. Here we present RAVEN Toolbox 2.0 with major enhancements, including: (i) de novo reconstruction of GEMs based on the MetaCyc pathway database; (ii) a redesigned KEGG-based reconstruction pipeline; (iii) convergence of reconstructions from various sources; (iv) improved performance, usability, and compatibility with the COBRA Toolbox. Capabilities of RAVEN 2.0 are here illustrated through de novo reconstruction of GEMs for the antibiotic-producing bacterium Streptomyces coelicolor. Comparison of the automated de novo reconstructions with the iMK1208 model, a previously published high-quality S. coelicolor GEM, exemplifies that RAVEN 2.0 can capture most of the manually curated model. The generated de novo reconstruction is subsequently used to curate iMK1208 resulting in Sco4, the most comprehensive GEM of S. coelicolor, with increased coverage of both primary and secondary metabolism. This increased coverage allows the use of Sco4 to predict novel genome editing targets for optimized secondary metabolites production. As such, we demonstrate that RAVEN 2.0 can be used not only for de novo GEM reconstruction, but also for curating existing models based on up-to-date databases. Both RAVEN 2.0 and Sco4 are distributed through GitHub to facilitate usage and further development by the community (https://github.com/SysBioChalmers/RAVEN and https://github.com/SysBioChalmers/Streptomyces_coelicolor-GEM).

Bioinformatics Support, Infrastructure and Training [Technology development]

Systems Biology [Technology development]

PubMed 30335785

DOI 10.1371/journal.pcbi.1006541

Crossref 10.1371/journal.pcbi.1006541

pii: PCOMPBIOL-D-18-00741
pmc: PMC6207324
figshare: 10.6084/m9.figshare.6236903