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ACS Synth Biol. 2016 Mar 18;5(3):250-8. doi: 10.1021/acssynbio.5b00202. Epub 2016 Jan 7.

Identifying Regulatory Changes to Facilitate Nitrogen Fixation in the Nondiazotroph Synechocystis sp. PCC 6803.

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Department of Chemical Engineering, Pennsylvania State University , University Park, Pennsylvania 16801, United States.
Cancer Informatics Core, H. Lee Moffitt Cancer Center and Research Institute , Tampa, Florida 33612, United States.
Department of Energy, Environmental, and Chemical Engineering, Washington University , St. Louis, Missouri 63130, United States.
Department of Biology, Washington University , St. Louis, Missouri 63130, United States.


The incorporation of biological nitrogen fixation into a nondiazotrophic photosynthetic organism provides a promising solution to the increasing fixed nitrogen demand, but is accompanied by a number of challenges for accommodating two incompatible processes within the same organism. Here we present regulatory influence networks for two cyanobacteria, Synechocystis PCC 6803 and Cyanothece ATCC 51142, and evaluate them to co-opt native transcription factors that may be used to control the nif gene cluster once it is transferred to Synechocystis. These networks were further examined to identify candidate transcription factors for other metabolic processes necessary for temporal separation of photosynthesis and nitrogen fixation, glycogen catabolism and cyanophycin synthesis. Two transcription factors native to Synechocystis, LexA and Rcp1, were identified as promising candidates for the control of the nif gene cluster and other pertinent metabolic processes, respectively. Lessons learned in the incorporation of nitrogen fixation into a nondiazotrophic prokaryote may be leveraged to further progress the incorporation of nitrogen fixation in plants.


Cyanothece; Synechocystis; computational biotechnology; cyanobacteria; gene regulatory network; modeling

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