Sanglifehrin A belongs to a novel family of immunophilin-binding ligands. Sanglifehrin A is similar to cyclosporin A in that it binds to cyclophilins. Unlike cyclosporin A, however, the cyclophilin-sanglifehrin A complex has no effect on the calcium-dependent protein phosphatase calcineurin. It has been previously shown that sanglifehrin A specifically blocks T cell proliferation in response to interleukin 2 by inhibiting the appearance of cell cycle kinase activity cyclinE-Cdk2. How sanglifehrin A treatment leads to the cell cycle blockade has remained unknown. We report that sanglifehrin A is capable of activating the tumor suppressor gene p53 at the transcription level, leading to up-regulation of p21 that then binds and inhibits the cylcinE-Cdk2 complex. Further analysis of different elements in the p53 promoter showed that sanglifehrin A activates p53 transcription primarily through the activation of the transcription factor NFB by activating IB kinase in a manner that is similar to several genotoxic agents. Unlike other genotoxic drugs, sanglifehrin A does not cause DNA damage, making it a unique natural product that is capable of activating the NFB signaling pathway without affecting DNA.The immunosuppressive drugs cyclosporin A, FK506, and rapamycin constitute a unique family of natural products that work by an unusual mechanism (1-8). They serve as natural dimerizers that bring together two proteins, suppressing the function of both proteins as a consequence. Thus, CsA 1 is known to bind to the cyclophilin family of proteins (9) while FK506 and rapamycin are known to bind to the FKBP family of proteins (10, 11). Each of the immunophilin-drug complexes specifically interacts with and inhibits the function of their ultimate target. The CsA-cyclophilin and the FKBP-FK506 complexes specifically inhibit the protein phosphatase calcineurin (12, 13) while the FKBP-rapamycin complex specifically inhibits the function of the protein known as FRAP/RAFT/ TOR (14 -18). Inhibition of the phosphatase activity of calcineurin prevents the dephosphorylation of a critical transcription factor, NFAT, thereby blocking the transcription of a number of cytokine genes (5, 8). The binding of FKBP-rapamycin to RRAP/RAFT/TOR interferes with the function of TOR, leading to a blockade of cell cycle at the G 1 phase of the cell cycle.Sanglifehrin A (SFA) is a new member of the immunophilin ligand superfamily. It was discovered through a screen for novel cyclophilin ligands that block T cell activation (19,20). Similar to CsA, SFA binds to cyclophilin with high affinity. Unlike CsA, however, the cyclophilin-SFA complex has no effect on the phosphatase activity of calcineurin (21). Although SFA was shown to inhibit mouse and human mixed lymphocyte reactions (19), we and others have recently found that SFA does not affect T cell receptor-mediated signal transduction pathways leading to the production of cytokines such as IL-2 (21, 22). Instead, SFA inhibits IL-2-dependent T cell proliferation, similar to rapamycin (23, 24). Moreover, ...

To improve the efficiency of simultaneous heterotrophic nitrification and aerobic denitrification (SND) at high concentrations of NaCl and ammonia nitrogen (NH-N), we investigated the SND characteristics of Halomonas bacteria with the ability to synthesize the compatible solute ectoine. Halomonas sp. strain B01, which was isolated, screened and identified in this study, could simultaneously remove nitrogen (N) by SND and synthesize ectoine under high NaCl conditions. Gene cloning and sequencing analysis indicated that this bacterial genome contains ammonia monooxygenase (amoA) and nitrate reductase (narH) genes. Optimal conditions for N removal in a solution containing 600 mg/L NH-N were as follows: sodium succinate supplied as organic carbon (C) source at a C/N ratio of 5, pH 8 and shaking culture at 90 rpm. The N removal rate was 96.0% under these conditions. The SND by Halomonas sp. strain B01 was performed in N removal medium containing 60 g/L NaCl and 4,000 mg/L NH-N; after 180 h the residual total inorganic N concentration was 21.7 mg/L and the N removal rate was 99.2%. Halomonas sp. strain B01, with the ability to synthesize the compatible solute ectoine, could simultaneously tolerate high concentrations of NaCl and NH-N and efficiently perform N removal by SND.

In this study, poly-β-hydroxybutyrate (PHB) was synthesized by moderately halophilic bacteria Halomonas venusta and identified by 1H-NMR. The effects of different carbon sources, salt concentration, initial carbon nitrogen quality ratio, initial phosphate concentration were studied on the synthesis of PHB. The optimum conditions of the PHB synthesis were detemined. Glucose was as carbon source with the concentration of 80 g/L and salt concentration, initial carbon nitrogen ratio, initial phosphate concentration was 3%, 15 and 1.9 g/L respectively. Under the above conditions, a two-phase synthesis system of PHB was constructed. The PHB synthesis amount and yield of cell dry weight was reached up to 1.5 g/L and 69.19 wt.%, respectively. The efficient synthesis of PHB was realized.

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Ectoine had important physiological functions and superior potential applications, so the study of ectoine was extensively attented. This article was related to kinetic models of cell growth, product formation and substrate consumption, which was not only established according to the characteristics of ectoine batch fermentation by Halomonas salina DSM 5928 but also obtained the kinetic parameters by the nonlinear fitting method in the Microcal Origin software. Logistic, Luedeking-Piret and Luedeking-Piret-like equations was applied to analyze the cell growth, the ectoine formation and the substrate consumption by the kinetic model，respectively. The results between calculated values and experimental data were coincident. By fitting, correlation coefficients R2 were ≥ 0.989. The fermentation conditions of ectoine were analyzed according to the model. The results showed that ectoine productivity (0.28 g/L/h) was the highest when initial monosodium glutamate concentration (S0) was 60 g/L. However, when S0 was 80 g/L, the ectoine concentration was maximal, i.e., 7.59 g/L. The research suggested that ectoine formation belonged to the mixed kinetic mechanism of cell growth and biomass concentration, while the ectoine production mainly depended on instantaneous biomass concentration. The fermentation method for improving ectoine concentration was further proved. The established kinetic model will be of significant value to provide the optimal conditions of present process.