Cross-feeding between cyanobacterium Synechococcus and Escherichia coli in an artificial autotrophic-heterotrophic coculture system revealed by integrated omics analysis.

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.

[Using OMICS technologies to analyze the mechanisms of synthetic microbial co-culture systems: a review].

In recent years, the interaction mechanisms underpinning the synthetic microbial co-culture systems have gained increasing attention due to their potentials in various biotechnological applications. Exploration of the inter-species mechanisms underpinning the synthetic microbial co-culture system could contribute to a better understanding of the theoretical basis to further optimize the existing co-culture systems, and design new synthetic co-culture system for large-scale application. OMICS technologies such as genomics, transcriptomics, proteomics, and metabolomics could analyze the biological processes in a high throughput manner. Multi-omics analysis could achieve a "global view" of various members in the microbial co-culture systems, which presents opportunities in understanding synthetic microbial consortia better. This article summarizes recent advances in understanding the mechanisms of synthetic microbial co-culture systems using omics technologies, from the aspects of metabolic network, energy metabolism, signal transduction, membrane transport, stress response, community stability and structural rationality. All these findings could provide important theoretical basis for future application of the microbial co-culture systems with the aids of emerging biotechnologies such as synthetic biology and genome editing.

Cellular engineering strategies toward sustainable omega-3 long chain polyunsaturated fatty acids production: State of the art and perspectives.

Long-chain polyunsaturated fatty acids (LC-PUFAs) especially ω-3 fatty acids provide significant health benefits for human beings. However, ω-3 LC-PUFAs cannot be synthesized de novo in mammals. Traditionally, ω-3 LC-PUFAs are extracted from marine fish, and their production depends on sea fishing, which has not met ever-increasing global demand. To address the challenges, innovative cellular engineering strategies need to be developed. In nature, many fungi and microalgae are rich in ω-3 LC-PUFAs, representing promising sources of ω-3 LC-PUFAs. The latest progress in developing new cellular engineering strategies toward sustainable ω-3 LC-PUFAs production using fungi and microalga has demonstrated that they can to some extent address the supply shortage. In this review, we critically summarize the recent progress in enhancing the productivity in various ω-3 LC-PUFAs-producing organisms, as well as the latest efforts of biosynthesizing PUFAs in heterogenous biosystems. In addition, we also provide future perspectives in developing genetic toolkits for LC-PUFAs producing microbes so that cut-edging biotechnology such as gene stacking and genome editing can be further applied to increase the productivity of ω-3 LC-PUFAs.