Cross-feeding between cyanobacterium Synechococcus and Escherichia coli in an artificial autotrophic–heterotrophic coculture system revealed by integrated omics analysis
Authors: Ma Jiajia , Guo Taohong , Ren Meijin , Chen Lei , Song Xinyu , Zhang Weiwen 
Published: June 2022

Abstract
Background
Light-driven consortia, which consist of sucrose-secreting cyanobacteria and heterotrophic species, have attracted considerable attention due to their capability for the sustainable production of valuable chemicals directly from CO2. In a previous study, we achieved a one-step conversion of sucrose secreted from cyanobacteria to fine chemicals by constructing an artificial coculture system consisting of sucrose-secreting Synechococcus elongateus cscB+ and 3-hydroxypropionic acid (3-HP) producing Escherichia coli ABKm. Analyses of the coculture system showed that the cyanobacterial cells grew better than their corresponding axenic cultures. To explore the underlying mechanism and to identify the metabolic nodes with the potential to further improve the coculture system, we conducted integrated transcriptomic, proteomic and metabolomic analyses.

Results
We first explored how the relieved oxidative stress affected cyanobacterial cell growth in a coculture system by supplementing additional ascorbic acid to CoBG-11 medium. We found that the cell growth of cyanobacteria was clearly improved with an additional 1 mM ascorbic acid under axenic culture; however, its growth was still slower than that in the coculture system, suggesting that the improved growth of Synechococcus cscB+ may be caused by multiple factors, including reduced oxidative stress. To further explore the cellular responses of cyanobacteria in the system, quantitative transcriptomics, proteomics and metabolomics were applied to Synechococcus cscB+. Analyses of differentially regulated genes/proteins and the abundance change of metabolites in the photosystems revealed that the photosynthesis of the cocultured Synechococcus cscB+ was enhanced. The decreased expression of the CO2 transporter suggested that the heterotrophic partner in the system might supplement additional CO2 to support the cell growth of Synechococcus cscB+. In addition, the differentially regulated genes and proteins involved in the nitrogen and phosphate assimilation pathways suggested that the supply of phosphate and nitrogen in the Co-BG11 medium might be insufficient.

Conclusion
An artificial coculture system capable of converting CO2 to fine chemicals was established and then analysed by integrated omics analysis, which demonstrated that in the coculture system, the relieved oxidative stress and increased CO2 availability improved the cell growth of cyanobacteria. In addition, the results also showed that the supply of phosphate and nitrogen in the Co-BG11 medium might be insufficient, which paves a new path towards the optimization of the coculture system in the future. Taken together, these results from the multiple omics analyses provide strong evidence that beneficial interactions can be achieved from cross-feeding and competition between phototrophs and prokaryotic heterotrophs and new guidelines for engineering more intelligent artificial consortia in the future.