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

Content Provider	Springer Nature Link
Author	Sengupta, Tirthankar Bhushan, Mani Wangikar, Pramod P.
Copyright Year	2013
Abstract	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.
Starting Page	155
Ending Page	165
Page Count	11
File Format	PDF
ISSN	01668595
Journal	Photosynthesis Research
Volume Number	118
Issue Number	1-2
e-ISSN	15735079
Language	English
Publisher	Springer Netherlands
Publisher Date	2013-11-05
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Flux balance analysis MOMA ROOM Ethanol Synechocystis Plant Sciences Plant Physiology Biochemistry Plant Genetics & Genomics
Content Type	Text
Resource Type	Article
Subject	Cell Biology Plant Science Medicine Biochemistry

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