Bioinformatics. 2018 Sep 01;34(17):i954-i963. doi: 10.1093/bioinformatics/bty561.
FLYCOP: metabolic modeling-based analysis and engineering microbial communities.
Bioinformatics (Oxford, England)
Beatriz García-Jiménez, José Luis García, Juan Nogales
Affiliations
Affiliations
- Department of Systems Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CNB-CSIC), 28049 Madrid, Spain.
- Microbial and Plant Biotechnology Department, Centro de Investigaciones Biológicas (CIB-CSIC), 28040 Madrid, Spain.
- Applied System Biology and Synthetic Biology Department, Institute for Integrative Systems Biology (I2Sysbio-CSIC-UV), 46980 Paterna, Spain.
PMID: 30423096
PMCID: PMC6129290 DOI: 10.1093/bioinformatics/bty561
Abstract
MOTIVATION: Synthetic microbial communities begin to be considered as promising multicellular biocatalysts having a large potential to replace engineered single strains in biotechnology applications, in pharmaceutical, chemical and living architecture sectors. In contrast to single strain engineering, the effective and high-throughput analysis and engineering of microbial consortia face the lack of knowledge, tools and well-defined workflows. This manuscript contributes to fill this important gap with a framework, called FLYCOP (FLexible sYnthetic Consortium OPtimization), which contributes to microbial consortia modeling and engineering, while improving the knowledge about how these communities work. FLYCOP selects the best consortium configuration to optimize a given goal, among multiple and diverse configurations, in a flexible way, taking temporal changes in metabolite concentrations into account.
RESULTS: In contrast to previous systems optimizing microbial consortia, FLYCOP has novel characteristics to face up to new problems, to represent additional features and to analyze events influencing the consortia behavior. In this manuscript, FLYCOP optimizes a Synechococcus elongatus-Pseudomonas putida consortium to produce the maximum amount of bio-plastic (PHA, polyhydroxyalkanoate), and highlights the influence of metabolites exchange dynamics in a four auxotrophic Escherichia coli consortium with parallel growth. FLYCOP can also provide an explanation about biological evolution driving evolutionary engineering endeavors by describing why and how heterogeneous populations emerge from monoclonal ones.
AVAILABILITY AND IMPLEMENTATION: Code reproducing the study cases described in this manuscript are available on-line: https://github.com/beatrizgj/FLYCOP.
SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
References
- Am Nat. 2000 Jan;155(1):24-35 - PubMed
- Nature. 2009 Oct 29;461(7268):1243-7 - PubMed
- Nature. 2017 Nov 2;551(7678):45-50 - PubMed
- Mol Syst Biol. 2011 Oct 11;7:535 - PubMed
- Environ Microbiol. 2016 Feb;18(2):341-57 - PubMed
- Metab Eng. 2016 Sep;37:114-121 - PubMed
- J Bacteriol. 2007 Jul;189(14):5142-52 - PubMed
- PLoS Comput Biol. 2017 May 22;13(5):e1005544 - PubMed
- Trends Biotechnol. 2008 Sep;26(9):483-9 - PubMed
- Front Microbiol. 2017 Nov 27;8:2299 - PubMed
- Microb Biotechnol. 2016 Sep;9(5):564-7 - PubMed
- Appl Environ Microbiol. 2012 Apr;78(8):2660-8 - PubMed
- Biotechnol Biofuels. 2016 Jan 22;9:17 - PubMed
- BMC Syst Biol. 2013 Aug 08;7:74 - PubMed
- Science. 2014 Mar 21;343(6177):1366-9 - PubMed
- Front Microbiol. 2016 May 18;7:673 - PubMed
- Curr Opin Biotechnol. 2017 Oct;47:67-82 - PubMed
- Nat Rev Genet. 2014 Feb;15(2):107-20 - PubMed
- Mol Syst Biol. 2007;3:121 - PubMed
- J R Soc Interface. 2016 Nov;13(124): - PubMed
- Curr Opin Biotechnol. 2017 Jun;45:85-91 - PubMed
- ACS Synth Biol. 2014 Apr 18;3(4):247-57 - PubMed
- J Theor Biol. 2008 Jun 7;252(3):497-504 - PubMed
- Biotechnol J. 2017 Mar;12(3): - PubMed
- Nat Protoc. 2011 Aug 04;6(9):1290-307 - PubMed
- Cell Rep. 2014 May 22;7(4):1104-15 - PubMed
- PLoS Comput Biol. 2017 May 15;13(5):e1005539 - PubMed
- BMC Evol Biol. 2016 Aug 20;16(1):163 - PubMed
- Sci Rep. 2016 Jul 04;6:29182 - PubMed
- Proc Natl Acad Sci U S A. 2012 Jun 12;109(24):9487-92 - PubMed
- Nat Rev Genet. 2010 May;11(5):367-79 - PubMed
- Microb Biotechnol. 2016 Sep;9(5):610-7 - PubMed
- Proc Natl Acad Sci U S A. 2016 Dec 20;113(51):E8344-E8353 - PubMed
- ACS Synth Biol. 2018 Apr 20;7(4):1163-1166 - PubMed
- Front Plant Sci. 2016 Sep 26;7:1421 - PubMed
- Elife. 2015 Oct 16;4:e08208 - PubMed
- Front Microbiol. 2017 May 10;8:827 - PubMed
- Environ Microbiol. 2017 Aug;19(8):2949-2963 - PubMed
- Bioinformatics. 2016 Jul 1;32(13):2008-16 - PubMed
- Biotechnol Adv. 2017 Nov 15;35(7):845-866 - PubMed
- J Bacteriol. 2012 Nov;194(21):5897-908 - PubMed
- Genome Biol. 2016 May 23;17(1):109 - PubMed
- Am Nat. 2017 Aug;190(S1):S57-S68 - PubMed
MeSH terms
Publication Types