Hendry, John I.; Prasannan, Charulata B.; Joshi, Aditi; Dasgupta, Santanu; Wangikar, Pramod P.
초록
<P><B>Abstract</B></P> <P>Flux Balance Analysis was performed with the Genome Scale Metabolic Model of a fast growing cyanobacterium <I>Synechococcus</I> sp. PCC 7002 to gain insights that would help in engineering the organism as a production host. Gene essentiality and synthetic lethality analysis revealed a reduced metabolic robustness under genetic perturbation compared to the heterotrophic bacteria <I>Escherichia coli</I>. Under glycerol heterotrophy the reducing equivalents were generated from tricarboxylic acid cycle rather than the oxidative pentose phosphate pathway. During mixotrophic growth in glycerol the photosynthetic electron transport chain was predominantly used for ATP synthesis with a photosystem I/photosystem II flux ratio higher than that observed under autotrophy. An exhaustive analysis of all possible double reaction knock outs was performed to reroute fixed carbon towards ethanol and butanol production. It was predicted that only ∼10% of fixed carbon could be diverted for ethanol and butanol production.</P> <P><B>Highlights</B></P> <P> <UL> <LI> An updated GENRE was developed for <I>Synechococcus</I> sp. PCC 7002. </LI> <LI> Only 45.7% of the metabolic genes were essential under all studied conditions. </LI> <LI> Under autotrophy TCA cycle was open and used to supply precursors for amino acids. </LI> <LI> TCA cycle was main source of reducing equivalents under glycerol heterotrophy. </LI> <LI> Double gene knock outs could divert only 10% of the fixed carbon. </LI> </UL> </P>