sysbiochalmers/rhto-gem

Genome-scale metabolic model of Rhodotorula toruloides

rhto-GEM: Genome-scale metabolic model of Rhodotorula toruloides

• Brief model description

This repository contains the updated genome-scale metabolic model of Rhodotorula toruloides, named rhto-GEM. For the latest updated release see here.

• Abstract

Rhodotorula toruloides (syn. Rhodosporidium toruloides) is a basidiomycetous yeast belonging to the subphylum Pucciniomycotina and occurs naturally in a wide range of habitats including surfaces of leaves, soil and sea water. The broad substrate range of R. toruloides and its ability to accumulate lipids exceeding half of its cell dry weight has made this yeast a popular system for production of biological oils from inedible substrates (e.g. pentose sugars, crude glycerol). The R. toruloides lipid fraction contains ω-3 linolenic acid and heptadecenoic acid, which makes this yeast a promising organism for production of pharma- and nutraceuticals. R. toruloides also produces a number of carotenoid pigments including torularhodin, torulene, γ-carotene and β-carotene. Other applications of R. toruloides include the production of the enzymes L-phenylalanine ammonia-lyase and D-amino acid oxidase.

• Model keywords

GEM category: Species; Utilisation: experimental data reconstruction; Field: metabolic-network reconstruction; Type of model: reconstruction, curated; Model source: yeast-GEM & iYali; Omic source: genomics; Taxonomy: Rhodotorula toruloides; Metabolic system: general metabolism; Bioreactor; Strain: NP11; Condition: minimal medium;

• Reference:

Tiukova IA, Prigent S, Nielsen J, Sandgren M & Kerkhoven EJ (2019) "Genome-scale model of Rhodotorula toruloides metabolism" Biotechnol Bioeng. doi:10.1002/bit.27162

Lopes HJS et al. "C/N ratio and carbon source-dependent lipid production profiling in Rhodotorula toruloides" Appl Microbiol Biotechnol. doi:10.1007/s00253-020-10386-5

• Last update: 2020-04-19

• Main model descriptors:

Taxonomy	Template Model	Reactions	Metabolites	Genes
Rhodotorula toruloides	yeast-GEM & iYali	2723	2277	832

A Memote snapshot report of the most recent release is available here.

This repository is administered by @edkerk, Division of Systems and Synthetic Biology, Department of Biology and Biological Engineering, Chalmers University of Technology.

Citation

• If you use rhto-GEM in your research, whether for simulations, data analysis, model reconstruction of other purposes, we ask you to cite the rhto-GEM paper on bioRxiv.
• In addition, it is good practice to cite the specific version of rhto-GEM that you used, to improve reproducibility. All rhto-GEM releases are archived in Zenodo. Find the corresponding DOI for each release here.

Installation

Required software

• This model is recommended to be used with the RAVEN toolbox for MATLAB (version 2.0).
• Alternatively, the model can also be directly used with the COBRA toolbox for MATLAB, cobrapy, or other software or toolboxes that support genome-scale models in SBML L3V1 FBCv2 format.

Dependencies

• Please see the RAVEN toolbox repository for dependencies regarding RAVEN.
• For contribution to development: a git wrapper added to the search path.

Installation instructions

• Just want to use the model? Clone it from master in the Github repo, or just download the latest release.
• Wish to also contribute? Fork it to your Github account, and create a new branch from devel.

Model files

The model is available in .xml, .txt, .yml, .mat and .xlsx (the last 2 extensions only in master). Additionally, versions of toolboxes & SBML used for saving the model are tracked in dependencies.txt.

Complementary scripts

• newCommit.m: prepares files from a modified model for a new GitHub commit in a development branch.
• newCommit.m: prepares files from a modified model for a new GitHub release in the master branch.
• Lopes2019: folder with scripts related to Lopes et al. (2019)
• analysis: folder with scripts performing analyses on rhto-GEM.
• curation: folder with additional curation scripts, after the initial reconstruction
• experimental: folder with scripts that modify rhto-GEM to incorporate experimental data.
• reconstruction: folder with scripts that detail the model reconstruction and curation process.
• validation: folder with scripts validating performance of rhto-GEM.

Complementary data

• Lopes2019: folder with data related to Lopes et al. (2019)
• data: experimentally measured data.
• genome: protein fasta files of R. toruloides, S. cerevisiae and Y. lipolytica, as used for identifying orthologs.
• meneco: input and output files for meneco, as run for r4_gapfilling.
• reconstruction: miscellaneous files used during model reconstruction.
• validation: experimental data used to validate rhto-GEM.

Contributors

• Ievgeniia Tiukova (@itaova), Chalmers University of Technology, Gothenburg Sweden
• Eduard J. Kerkhoven (@edkerk), Chalmers University of Technology, Gothenburg Sweden

rhto-gem's Issues

feat: continuous integration with memote

bug: duplicate reactions

During reconstruction, duplicate reactions were added, sometimes with alternative reversibility. These should be manually curated.

To check:

• r_0104 & t_0052
• r_3510 & t_0871
• r_3512 & t_0872
• r_3513 & t_0873
• r_3608 & t_0876
• r_3610 & t_0877
• r_3611 & t_0878

chore: convert to standard-GEM

Follow the standard from https://github.com/MetabolicAtlas/standard-GEM

• reorganize files and folders
• restructure README.md

bug: duplicate grRule

Reaction r_0438 has duplicates in its grRule, with identical sets of subunits. The grRule is here split:

• (COX1 and COX2 and COX3 and RHTO_00755 and RHTO_05208 and RHTO_04577 and RHTO_01605 and RHTO_03666 and RHTO_01854 and RHTO_06415 and RHTO_06298 and RHTO_04910) or
• (COX1 and COX2 and COX3 and RHTO_00755 and RHTO_05208 and RHTO_04577 and RHTO_01605 and RHTO_03666 and RHTO_06415 and RHTO_06298 and RHTO_04910 and RHTO_01854) or
• (COX1 and COX2 and COX3 and RHTO_00755 and RHTO_04577 and RHTO_01605 and RHTO_03666 and RHTO_01854 and RHTO_05208 and RHTO_06415 and RHTO_06298 and RHTO_04910) or
• (COX1 and COX2 and COX3 and RHTO_00755 and RHTO_04577 and RHTO_01605 and RHTO_03666 and RHTO_05208 and RHTO_06415 and RHTO_06298 and RHTO_04910 and RHTO_01854)

and all four sets are basically the same.

bug: incorrect isoenzymes annotated

In the reconstruction pipeline, the parameters used in getModelFromHomology might have been a bit too lenient resulting in more gene alternative genes included in various grRules. Particularly, sometimes there is an orthologous gene found with very high scores (the obvious ortholog), while there is also another hit that is just above the cut-off. These low-scoring hits in presence of an obvious ortholog are most likely false and should be left out. Fixing this requires manual curation.