Integrated proteomic and metabolomic analysis of a reconstructed three-species microbial consortium for one-step fermentation of 2-keto-L-gulonic acid, the precursor of vitamin C.

Microbial consortia, with the merits of strong stability, robustness, and multi-function, played critical roles in human health, bioenergy, and food manufacture, etc. On the basis of 'build a consortium to understand it', a novel microbial consortium consisted of Gluconobacter oxydans, Ketogulonicigenium vulgare and Bacillus endophyticus was reconstructed to produce 2-keto-L-gulonic acid (2-KGA), the precursor of vitamin C. With this synthetic consortium, 73.7 g/L 2-KGA was obtained within 30 h, which is comparable to the conventional industrial method. A combined time-series proteomic and metabolomic analysis of the fermentation process was conducted to further investigate the cell-cell interaction. The results suggested that the existence of B. endophyticus and G. oxydans together promoted the growth of K. vulgare by supplying additional nutrients, and promoted the 2-KGA production by supplying more substrate. Meanwhile, the growth of B. endophyticus and G. oxydans was compromised from the competition of the nutrients by K. vulgare, enabling the efficient production of 2-KGA. This study provides valuable guidance for further study of synthetic microbial consortia.

Tanshinone IIA derivatives induced S-phase arrest through stabilizing c-myc G-quadruplex DNA to regulate ROS-mediated PI3K/Akt/mTOR pathway.

Herein, a derivate from tanshinone IIA, 1,6,6-trimethyl-11-phenyl-7,8,9,10-tetrahydro-6H-furo[2',3':1,2]phenanthro[3,4-d]imidazole (TA25), has been synthesized and investigated as potential inhibitor against the proliferation, migration and invasion of lung cancer cells. MTT assay and cell colony formation assay results showed that TA25 exhibits acceptable inhibitory effect against the proliferation of lung cancer A549 cells, and the value of IC50 was about 17.9 µM. This result was further confirmed by the inhibition of TA25 against the growth of xenograft lung cancer cells on zebrafish bearing tumor (A549 lung cancer cells). The results of wound-healing assay and FITC-gelatin invasion assay displayed that TA25 could inhibit the migration and invasion of lung cancer A549 cells. Moreover, the studies on the binding properties of TA25 interact with c-myc G-quadruplex DNA suggested that TA25 can bind in the G-quarter plane formed from G7, G11, G16 and G20 with c-myc G-quadruplex DNA through π-π stacking. Further study of the potential anti-cancer mechanism indicated that TA25 can induce S-phase arrest in lung cancer A549 cells, and this phenomenon resulted from the promotion of the production of reactive oxygen species and DNA damage in A549 cells under the action of TA25. Further research revealed that TA25 could inhibit the PI3K/Akt/mTOR signal pathway and increase the expression of p53 protein. Overall, TA25 can be developed into a promising inhibitor against the proliferation, migration and invasion of lung cancer cells and has potential clinical application in the near future.