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ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Microbial Physiology and Metabolism
Volume 16 - 2025 | doi: 10.3389/fmicb.2025.1556583
Site-2 protease Sll0528 interacts with RbcR to regulate carbon/nitrogen homeostasis in the Cyanobacterium Synechocystis sp. PCC 6803
Provisionally accepted- South China University of Technology, Guangzhou, China
Cyanobacteria play pivotal roles in global biogeochemical cycles through oxygenic photosynthesis. To maintain cellular homeostasis, these organisms employ sophisticated acclimation mechanisms to adapt to environmental fluctuations, particularly nitrogen availability. While nitrogen deprivation triggers dormancy, excess ammonium exerts toxic effects on cyanobacteria and other photosynthetic organismsa phenomenon whose acclimation mechanisms remain poorly understood. Through physiological characterization of knockout and overexpression mutants in Synechocystis sp. PCC 6803, we identified the site-2 protease Sll0528 as a critical regulator of ammonium stress acclimation. TurboID based proximity labeling coupled with quantitative proteomics revealed a robust set of putative Sll0528 interacting proteins, some of which were subsequently validated through bacterial two hybrid assays and transcriptomic profiling. Notably, we confirmed the physical interaction between Sll0528 and RbcR, the low carbon responsive transcriptional regulator.Transcriptomic analysis revealed that knockout of sll0528 led to significant downregulation of the RbcR regulon including the ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) operon rbcLXS. Further analysis suggests that this downregulation might be due to improper posttranscriptional regulation of RbcR, which depends on its interaction with Sll0528. Our findings reveal novel regulatory crosstalk between a cyanobacterial S2P protease and the carbon-responsive transcriptional machinery, providing new mechanistic insights into cyanobacterial carbon-nitrogen homeostasis control during nitrogen fluctuations. This study provides insights for the functional characterization of other S2P proteases in photosynthetic organisms and may facilitate cyanobacteria-based bioremediation of ammonium-rich wastewater.
Keywords: Cyanobacteria, Proximity labeling, Site-2 protease, Sll0528, RbcR, Synechocystis
Received: 07 Jan 2025; Accepted: 19 Mar 2025.
Copyright: © 2025 Lin, Zheng, Mo, Zhang and CHEN. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Gu CHEN, South China University of Technology, Guangzhou, China
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