OptFlux: an open-source software platform for in silico metabolic engineering.
BACKGROUND
Over the last few years a number of methods have been proposed for the phenotype simulation of microorganisms under different environmental and genetic conditions. These have been used as the basis to support the discovery of successful genetic modifications of the microbial metabolism to address industrial goals. However, the use of these methods has been restricted to bioinformaticians or other expert researchers. The main aim of this work is, therefore, to provide a user-friendly computational tool for Metabolic Engineering applications.


RESULTS
OptFlux is an open-source and modular software aimed at being the reference computational application in the field. It is the first tool to incorporate strain optimization tasks, i.e., the identification of Metabolic Engineering targets, using Evolutionary Algorithms/Simulated Annealing metaheuristics or the previously proposed OptKnock algorithm. It also allows the use of stoichiometric metabolic models for (i) phenotype simulation of both wild-type and mutant organisms, using the methods of Flux Balance Analysis, Minimization of Metabolic Adjustment or Regulatory on/off Minimization of Metabolic flux changes, (ii) Metabolic Flux Analysis, computing the admissible flux space given a set of measured fluxes, and (iii) pathway analysis through the calculation of Elementary Flux Modes. OptFlux also contemplates several methods for model simplification and other pre-processing operations aimed at reducing the search space for optimization algorithms. The software supports importing/exporting to several flat file formats and it is compatible with the SBML standard. OptFlux has a visualization module that allows the analysis of the model structure that is compatible with the layout information of Cell Designer, allowing the superimposition of simulation results with the model graph.


CONCLUSIONS
The OptFlux software is freely available, together with documentation and other resources, thus bridging the gap from research in strain optimization algorithms and the final users. It is a valuable platform for researchers in the field that have available a number of useful tools. Its open-source nature invites contributions by all those interested in making their methods available for the community. Given its plug-in based architecture it can be extended with new functionalities. Currently, several plug-ins are being developed, including network topology analysis tools and the integration with Boolean network based regulatory models.
Rocha
Isabel
I
IBB-Institute for Biotechnology and Bioengineering/Centre of Biological Engineering, University of Minho, 4710-057 Campus de Gualtar, Braga, Portugal. irocha@deb.uminho.pt
Maia
Paulo
P
Evangelista
Pedro
P
Vilaça
Paulo
P
Soares
Simão
S
Pinto
José P
JP
Nielsen
Jens
J
Patil
Kiran R
KR
Ferreira
Eugénio C
EC
Rocha
Miguel
M
D000465:Algorithms; D001419:Bacteria / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism; D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D004926:Escherichia coli / Q000235:genetics*; D019143:Evolution, Molecular; D053858:Metabolic Networks and Pathways; D008954:Models, Biological; D008957:Models, Genetic; D008962:Models, Theoretical; D010641:Phenotype; D011381:Programming Languages; D025941:Protein Interaction Mapping; D012984:Software
D001426:Bacterial Proteins
BMC Bioinformatics. 2007 Aug 28;8:313
17725829
Curr Opin Biotechnol. 2004 Feb;15(1):64-9
15102469
BMC Syst Biol. 2008 Jun 29;2:55
18588708
BMC Bioinformatics. 2005 Dec 23;6:308
16375763
Environ Microbiol. 2002 Mar;4(3):133-40
12000313
Proc Natl Acad Sci U S A. 2005 May 24;102(21):7695-700
15897462
Methods Mol Biol. 2008;416:409-31
18392985
Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):15112-7
12415116
Bioinformatics. 2003 Nov 1;19(16):2144-6
14594721
Bioinformatics. 2006 Aug 1;22(15):1930-1
16731697
Nucleic Acids Res. 2000 Jan 1;28(1):27-30
10592173
Bioinformatics. 2003 Mar 1;19(4):524-31
12611808
Biotechnol Adv. 2005 Nov;23(7-8):471-99
15919172
Bioinformatics. 2008 Oct 1;24(19):2229-35
18676417
Trends Biotechnol. 2007 Mar;25(3):119-24
17234288
BMC Bioinformatics. 2008 Nov 27;9:499
19038030
Biotechnol Bioeng. 2005 Jan 20;89(2):148-56
15543598
Nucleic Acids Res. 2006 Jan 1;34(Database issue):D689-91
16381960
Nature. 2002 Nov 14;420(6912):186-9
12432395
Nat Protoc. 2007;2(3):727-38
17406635
Genome Inform. 2002;13:214-23
14571390
Bioinformatics. 2008 Mar 15;24(6):880-1
18252737
Metab Eng. 2001 Apr;3(2):111-4
11289787
BMC Bioinformatics. 2006 Mar 13;7:129
16533403
Genome Res. 2003 Nov;13(11):2498-504
14597658
Bioinformatics. 2003 Jan 22;19(2):261-9
12538248
Nat Biotechnol. 2000 Mar;18(3):326-32
10700151
Genome Biol. 2003;4(9):R54
12952533
Nat Biotechnol. 2005 Aug;23(8):961-6
16082367
BMC Syst Biol. 2007 Jan 08;1:2
17408509
Biotechnol Bioeng. 2003 Dec 20;84(6):647-57
14595777
Bioinformatics. 2010 Feb 15;26(4):536-43
20031969
Trends Biotechnol. 2007 Mar;25(3):132-7
17254656