Enantioselective synthesis of (R)-phenylephrine by Serratia marcescens BCRC10948 cells that homologously express SM_SDR.

A short-chain dehydrogenase/reductase from Serratia marcescens BCRC10948, SM_SDR, has been cloned and expressed in Escherichia coli for the bioconversion of 1-(3-hydroxyphenyl)-2-(methylamino) ethanone (HPMAE) to (R)-phenylephrine[(R)-PE]. However, only 5.11mM (R)-PE was obtained from 10mM HPMAE after a 9h conversion in the previous report. To improve the biocatalytic efficiency, the homologous expression of the SM_SDR in S. marcescens BCRC10948 was achieved using the T5 promoter for expression. By using 2% glycerol as carbon source, we found that 8.00±0.15mM of (R)-PE with more than 99% enantiomeric excess was produced from 10mM HPMAE after 12h conversion at 30°C and pH 7.0. More importantly, by using 50mM HPMAE as the substrate, 23.78±0.84mM of (R)-PE was produced after a 12h conversion with the productivity and the conversion yield of 1.98mmol (R)-PE/lh and 47.50%, respectively. The recombinant S. marcescens cells could be recycled 6 times for the production of (R)-PE, and the bioconversion efficiency remained at 85% when compared to that at the first cycle. Our data indicated that a high conversion efficiency of HPMAE to (R)-PE could be achieved using S. marcescens BCRC10948 cells that homologously express the SM_SDR.

[Clinical analysis of value of different modes of respiratory support in the treatment of critical patients].

OBJECTIVE: To investigate the relationship between the successful results with different methods and time of initiation of respiratory support in critically ill patients. METHODS: The clinical data of 458 critical care patients were reviewed and analyzed. Among the patients, there were 47 cases of cardio-pulmonary resuscitation, 105 cases of acute airway obstruction, 156 cases of acute respiratory failure, and 150 cases of chronic respiratory failure. Intubation, or tracheostomy, or non-invasive positive pressure ventilation (NPPV) at different times and occasions were performed in the patients. RESULTS: One hundred and seventeen cases (25.5%) died during the respiratory support treatment, 49 cases gave up the treatment, and 292 patients (63.8%) were cured after mechanical ventilation. As the success rate was the lowest in patients who survived cardio-pulmonary resuscitation (21.3%, 10/47), it was higher in acute respiratory failure (55.1%, 86/156), and the best result (82.8%, 87/105) was obtained in the acute airway obstruction group and patients with chronic respiratory failure (72.7%, 109/150). In the group of patients undergoing early respiratory support, the cure rate was 95.0% (57/60) in patients with invasive method, and 95.5% (21/22) in the NPPV group. The result was significantly different compared with that of later treatment group [81.7% (68/82) in invasive group, and 60.9% (2/29) in NPPV group, both P<0.01]. It demonstrated that the earlier the respiratory support was given the better results. If the respiratory support was delayed, cure rate was significantly reduced [65.6% (63/96) in invasive group and 48.1% (13/27) in NPPV group, both P<0.01]. The cure rate was no difference between different modes of respiratory support between early treatment groups, however, invasive respiratory support was much better than NPPV [44.4% (40/90) and 0 (0/5)] when instituted in the late stages (all P<0.01). CONCLUSION: It is of prime importance to ensure optimal ventilation in the early stage of diseases, the difficulty and risk of establishment of a patent airway are main problems in the treatment of critically ill patients.