Metabolic Engineering of Shikimic Acid Biosynthesis Pathway for the Production of Shikimic Acid and Its Branched Products in Microorganisms: Advances and Prospects.

The shikimate pathway is a necessary pathway for the synthesis of aromatic compounds. The intermediate products of the shikimate pathway and its branching pathway have promising properties in many fields, especially in the pharmaceutical industry. Many important compounds, such as shikimic acid, quinic acid, chlorogenic acid, gallic acid, pyrogallol, catechol and so on, can be synthesized by the shikimate pathway. Among them, shikimic acid is the key raw material for the synthesis of GS4104 (Tamiflu®), an inhibitor of neuraminidase against avian influenza virus. Quininic acid is an important intermediate for synthesis of a variety of raw chemical materials and drugs. Gallic acid and catechol receive widespread attention as pharmaceutical intermediates. It is one of the hotspots to accumulate many kinds of target products by rationally modifying the shikimate pathway and its branches in recombinant strains by means of metabolic engineering. This review considers the effects of classical metabolic engineering methods, such as central carbon metabolism (CCM) pathway modification, key enzyme gene modification, blocking the downstream pathway on the shikimate pathway, as well as several expansion pathways and metabolic engineering strategies of the shikimate pathway, and expounds the synthetic biology in recent years in the application of the shikimate pathway and the future development direction.

[Efficacy of tyrosine kinase inhibitor in treatment of chronic myeloid leukemia patients].

OBJECTIVE: To evaluate the effects of tyrosine kinase inhibitors (TKI) in the treatment of chronic myeloid leukemia. METHODS: There were total 655 cases of chronic myeloid leukemia treated in one single-institution enrolled in this study. The dosage of TKI Imatinib was 400 mg/d for chronic phase, 600 mg/d for accelerated and blast phase respectively. Complete blood count, cytogenetic and molecular studies were regularly monitored during the course of therapy. The therapeutic effect was evaluated and the survival analysis was performed. RESULTS: The total complete hematologic response (CHR), major cytogenetic response (MCyR), complete cytogenetic response (CCyR) and major molecular response (MMR) rates were 92.1%, 75.8%, 73.1% and 47.9% respectively. 1-year, 3-year, 5-year and 10-year overall survival (OS) rates were (96.3 +/- 0.8)%, (86.3 +/-1.8)%, (79.0 +/- 2.4)% and (66.5 +/- 4.8)% respectively. 1 year, 3-year, 5-year and 10-year event-free survival (EFS) rates were (92.2 +/- 1.1)%, (77.9 +/- 2.1)%, (67.9 +/- 6.8)% and (35.8 +/- 6.0)% respectively. The proportion of the patients in chronic phase achieving CHR, MCyR, CCyR and MMR were 98.7%, 82.5%, 79.4% and 52.4% respectivly. Compared with chronic phase patients, the efficacy of IM in the treatment of accelerated phase and blast phase patients was significantly lower. The effect of TKI in early chronic phase was better than that in late chronic phase. Early molecular response was associated with a better 5-year EFS, but not OS. CONCLUSION: CML patients in chronic phase treated with TKI have a better outcome. The earlier TKI be used, the better the prognosis and efficacy be achieved.

[Cultivating an oleaginous microalgae with municipal wastewater].

Municipal wastewater is usually problematic for the environment. The process of oleaginous microalgal culture requires large amounts of nutrients and water. Therefore, we studied the feasibility of oleaginous microalgal culture of Scenedesmus dimorphus in bubbled column photobioreactor with municipal wastewater added with different nutrients. S. dimorphus could adapt municipal nutrient-rich wastewater by adding some nutrients as nitrogen, phosphorus, ferric ammonium citrate and trace elements, and the amounts of such nutrients have significant effects on cell growth, biomass yield and lipid accumulation. At optimum compositions of wastewater medium, the algal cell concentration could reach 8.0 g/L, higher than that of 5.0 g/L in standard BG11. Furthermore, S. dimorphus had strong capacity to absorb inorganic nitrogen and phosphorus from its culture water. There was almost no total nitrogen and phosphorus residues in culture medium after three or four days culturing when the adding mounts of nitrate and phosphate in wastewater medium were no more than 185.2 mg/L and 16.1 mg/L respectively under the experimental conditions. As a conclusion, it was feasible to cultivate oleaginous microalgae with municipal nutrient-rich wastewater, not only producing feedstock for algal biodiesel, but also removing inorganic nitrogen and phosphorus from wastewater.