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Metabolic modeling for multi-objective optimization of ethanol production in a Synechocystis mutant

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Title Metabolic modeling for multi-objective optimization of ethanol production in a Synechocystis mutant
 
Creator SENGUPTA, T
BHUSHAN, M
WANGIKAR, PP
 
Subject Flux balance analysis
MOMA
ROOM
Ethanol
Synechocystis
FLUX BALANCE ANALYSIS
PHOTOSYNTHETIC PRODUCTION
CYANOBACTERIA
OPTIMALITY
 
Description Cyanobacteria have potential to produce drop-in bio-fuels such as ethanol via photoautotrophic metabolism. Although model cyanobacterial strains have been engineered to produce such products, systematic metabolic engineering studies to identify optimal strains for the same have not been performed. In this work, we identify optimal ethanol producing mutants corresponding to appropriate gene deletions that result in a suitable redirection in the carbon flux. In particular, we systematically simulate exhaustive single and double gene deletions considering a genome scale metabolic model of a mutant strain of the unicellular cyanobacterium Synechocystis species strain PCC 6803. Various optimization based metabolic modeling techniques, such as flux balance analysis (FBA), method of minimization of metabolic adjustment (MOMA) and regulatory on/off minimization (ROOM) were used for this analysis. For single gene deletion MOMA simulations, the Pareto front with biomass and ethanol fluxes as the two objectives to be maximized was obtained and analyzed. Points on the Pareto front represent maximal utilization of resources constrained by substrate uptake thereby representing an optimal trade-off between the two fluxes. Pareto analysis was also performed for double gene deletion MOMA and single and double gene deletion ROOM simulations. Based on these analyses, two mutants, with combined gene deletions in ethanol and purine metabolism pathways, were identified as promising candidates for ethanol production. The relevant genes were adk, pta and ackA. An ethanol productivity of approximately 0.15 mmol/(gDW h) was predicted for these mutants which appears to be reasonable based on experimentally reported values in literature for other strains.
 
Publisher SPRINGER
 
Date 2014-10-15T08:42:31Z
2014-10-15T08:42:31Z
2013
 
Type Article
 
Identifier PHOTOSYNTHESIS RESEARCH, 118(1-2)155-165
0166-8595
1573-5079
http://dx.doi.org/10.1007/s11120-013-9935-x
http://dspace.library.iitb.ac.in/jspui/handle/100/14711
 
Language en