The microbial production of D-lysine to replace chemical approach has gained great interest with the rising concerns over the environment.Here,we employed recombinant E.coli strain BL21-LYR with lysine racemase and st...The microbial production of D-lysine to replace chemical approach has gained great interest with the rising concerns over the environment.Here,we employed recombinant E.coli strain BL21-LYR with lysine racemase and strain BL-22A-RB-YB with L-lysine monooxygenase and 5-aminovaleramide amidohydrolase to establish a two-strain coupling whole-cell bioconversion system for D-lysine production from L-lysine.To improve the optical purity of D-lysine,the optimal reaction condition for resolution of DL-lysine after the racemization was investigated.The specificity of BL-22A-RB-YB for L^-lysine and the effects of reaction condition on bioconversion efficiency of whole-cell were accordingly determined.Under the optimal condition,a maximum 53.5 g·L^-1 D-lysine and 48.2 g·L^-15-AVA were obtained with yield of 47.4%and 42.3%,respectively,by the microbial racemization and asymmetric degradation process.The final D-lysine enantiomeric excess was over 99%.Meanwhile,a valuable compound 5-aminovaleric acid was synthesized with the production of D-lysine,indicating the economic feasibility of the two-strain coupling system.展开更多
目的·探讨血糖控制不理想对2型糖尿病(type 2 diabetes mellitus,T2DM)患者亚临床心脏收缩功能的影响。方法·选取2021年6月—2022年3月于上海市第一人民医院嘉定分院随诊治疗的T2DM患者83例,以糖化血红蛋白(hemoglobin A1c,Hb...目的·探讨血糖控制不理想对2型糖尿病(type 2 diabetes mellitus,T2DM)患者亚临床心脏收缩功能的影响。方法·选取2021年6月—2022年3月于上海市第一人民医院嘉定分院随诊治疗的T2DM患者83例,以糖化血红蛋白(hemoglobin A1c,HbA1c)水平分为血糖控制理想(satisfactory control of glycaemia group,SCG)组和血糖控制不理想(less satisfactory control of glycaemia group,LSCG)组,同时选取对照组受试者54例。标准的超声心动图检查后,分别获取左心室结构和功能参数及左室心内膜下层、心肌中层和心外膜下层整体纵向应变(global longitudinal strain,GLS)指标GLS_(endo)、GLS_(mid)和GLS_(epi)。采用方差分析进行参数比较,相关分析采用Pearson相关分析和多元线性回归分析。应用受试者操作特征(receiver operator characteristic,ROC)曲线分析纵向应变以鉴别T2DM患者亚临床心肌功能损害的诊断效能。结果·室间隔厚度和左室后壁厚度在LSCG组均厚于SCG组和对照组(均P<0.05),而在SCG组和对照组间差异无统计学意义(均P>0.05)。与对照组相比,LSCG组和SCG组的左室舒张功能指标二尖瓣口舒张早期血流速度(early peak flow velocity by Doppler,E)/左心室侧壁二尖瓣环舒张早期运动速度(early diastolic velocity of the mitral annulus by tissue Doppler imaging,e)均较大且差异具有统计学意义(均P<0.05),而LSCG和SCG组间的差异无统计学意义(P>0.05)。左心室射血分数在3组间差异无统计学意义(P>0.05)。与LSCG组比较,GLS_(endo)、GLS_(mid)、GLS_(epi)的收缩形变数值在SCG组和对照组均较大(均P<0.05),而在SCG和对照组间差异无统计学意义(P>0.05)。HbA1c是GLS_(mid)和GLS_(epi)的独立负相关影响因素(β值分别为−0.198和−0.239,均P<0.05)。GLS_(endo)、GLS_(mid)和GLS_(epi)在LSCG与SCG组间具有中等诊断效能,曲线下面积(area under the curve,AUC)分别为0.754(95%CI 0.624~0.884)、0.755(95%CI 0.624~0.885)和0.751(95%CI 0.619~0.882)。结论·血糖控制不理想的T2DM患者心肌收缩功能减低,这种亚临床心肌损害与HbA1c水平呈独立负相关。展开更多
基金financial supports from the National Natural Science Foundation of China(Grant No.21908099)the National Key Research and Development Program of China(Grant No.2016YFA0204300)+2 种基金Key Research and Development Program(Social Development)Project Jiangsu Province(Grant No.BE2018730)the Natural Science Research Projects of Colleges and Universities in Jiangsu Province(Grant No.18KJB530009)the Jiangsu Synergetic Innovation Center for Advanced Bio-Manufacture(Grant No.XTB1802,Grant No.XTE1846)。
文摘The microbial production of D-lysine to replace chemical approach has gained great interest with the rising concerns over the environment.Here,we employed recombinant E.coli strain BL21-LYR with lysine racemase and strain BL-22A-RB-YB with L-lysine monooxygenase and 5-aminovaleramide amidohydrolase to establish a two-strain coupling whole-cell bioconversion system for D-lysine production from L-lysine.To improve the optical purity of D-lysine,the optimal reaction condition for resolution of DL-lysine after the racemization was investigated.The specificity of BL-22A-RB-YB for L^-lysine and the effects of reaction condition on bioconversion efficiency of whole-cell were accordingly determined.Under the optimal condition,a maximum 53.5 g·L^-1 D-lysine and 48.2 g·L^-15-AVA were obtained with yield of 47.4%and 42.3%,respectively,by the microbial racemization and asymmetric degradation process.The final D-lysine enantiomeric excess was over 99%.Meanwhile,a valuable compound 5-aminovaleric acid was synthesized with the production of D-lysine,indicating the economic feasibility of the two-strain coupling system.
文摘目的·探讨血糖控制不理想对2型糖尿病(type 2 diabetes mellitus,T2DM)患者亚临床心脏收缩功能的影响。方法·选取2021年6月—2022年3月于上海市第一人民医院嘉定分院随诊治疗的T2DM患者83例,以糖化血红蛋白(hemoglobin A1c,HbA1c)水平分为血糖控制理想(satisfactory control of glycaemia group,SCG)组和血糖控制不理想(less satisfactory control of glycaemia group,LSCG)组,同时选取对照组受试者54例。标准的超声心动图检查后,分别获取左心室结构和功能参数及左室心内膜下层、心肌中层和心外膜下层整体纵向应变(global longitudinal strain,GLS)指标GLS_(endo)、GLS_(mid)和GLS_(epi)。采用方差分析进行参数比较,相关分析采用Pearson相关分析和多元线性回归分析。应用受试者操作特征(receiver operator characteristic,ROC)曲线分析纵向应变以鉴别T2DM患者亚临床心肌功能损害的诊断效能。结果·室间隔厚度和左室后壁厚度在LSCG组均厚于SCG组和对照组(均P<0.05),而在SCG组和对照组间差异无统计学意义(均P>0.05)。与对照组相比,LSCG组和SCG组的左室舒张功能指标二尖瓣口舒张早期血流速度(early peak flow velocity by Doppler,E)/左心室侧壁二尖瓣环舒张早期运动速度(early diastolic velocity of the mitral annulus by tissue Doppler imaging,e)均较大且差异具有统计学意义(均P<0.05),而LSCG和SCG组间的差异无统计学意义(P>0.05)。左心室射血分数在3组间差异无统计学意义(P>0.05)。与LSCG组比较,GLS_(endo)、GLS_(mid)、GLS_(epi)的收缩形变数值在SCG组和对照组均较大(均P<0.05),而在SCG和对照组间差异无统计学意义(P>0.05)。HbA1c是GLS_(mid)和GLS_(epi)的独立负相关影响因素(β值分别为−0.198和−0.239,均P<0.05)。GLS_(endo)、GLS_(mid)和GLS_(epi)在LSCG与SCG组间具有中等诊断效能,曲线下面积(area under the curve,AUC)分别为0.754(95%CI 0.624~0.884)、0.755(95%CI 0.624~0.885)和0.751(95%CI 0.619~0.882)。结论·血糖控制不理想的T2DM患者心肌收缩功能减低,这种亚临床心肌损害与HbA1c水平呈独立负相关。