Nocathiacin I, a glycosylated thiopeptide antibiotic, displays excellent antibacterial activities against multidrug resistant bacterial pathogens. Previously, a novel nocathiacin I formulation for intravenous administ...Nocathiacin I, a glycosylated thiopeptide antibiotic, displays excellent antibacterial activities against multidrug resistant bacterial pathogens. Previously, a novel nocathiacin I formulation for intravenous administration has been successfully developed and its aqueous solubility is greatly enhanced for clinical application. The purpose of the present study was to increase the fermentation titer of nocathiacin I and reduce or eliminate analogous impurities by screening the medium ingredients using response surface methodology. After a sysmatic optimization, a water-soluble medium containing quality-controllable components was developed and validated, resulting in an increase in the production of nocathiacin I from 150 to 405.8 mg·L-1 at 150-L scale. Meanwhile, the analogous impurities existed in reported processes were greatly reduced or eliminated. Using optimized medium for fermentation, nocathiacin I with pharmaceutically acceptable quality was easily obtained with a recovery of 67%. In conclusion, the results from the present study offer a practical and efficient fermentation process for the production of nocathiacin I as a therapeutic agent.展开更多
The goal of this study was to use statistical optimization to change the nutritional and environmental conditions so that Streptomyces baarensis MH-133 could make more active metabolites.Twelve trials were used to scr...The goal of this study was to use statistical optimization to change the nutritional and environmental conditions so that Streptomyces baarensis MH-133 could make more active metabolites.Twelve trials were used to screen for critical variables influencing productivity using the Placket-Burman Design method.S.baarensis MH-133 is significantly influenced by elicitation,yeast extract,inoculum size,and incubation period in terms of antibacterial activity.A total of 27 experimental trials with various combinations of these factors were used to carry out the response surface technique using the Box-Behnken design.The analyses revealed that the model was highly significant(p<0.001),with a lack-of-fit of 0.212 and a coefficient determination(R2)of 0.9224.Additionally,the model predicted that the response as inhibition zone diameter would reach a value of 27 mm.Under optimal conditions,S.baarensis MH-133 produced 18.0 g of crude extract to each 35L and was purified with column chromatography.The active fraction exhibiting antibacterial activity was characterized using spectroscopic analysis.The MIC and MBC values varied between 37.5 and 300μg/ml and 75 and 300μg/ml,respectively.In conclusion,the biostatistical optimization of the active fraction critical variables,including environmental and nutritional conditions,enhances the production of bioactive molecules by Streptomyces species.展开更多
Response surface methodology(RSM)and artificial neural networks(ANN)are considered the most efficient way for opti-mization and modeling studies to design and develop various biosimilars.The primary objective of this ...Response surface methodology(RSM)and artificial neural networks(ANN)are considered the most efficient way for opti-mization and modeling studies to design and develop various biosimilars.The primary objective of this study was to create empirical modeling and optimization of media parameters for producing B.halotolerans VSH 09 lipase using RSM and ANN.One-factor-at-a-time(OFAT)analysis revealed that triacylglycerols hydrolyzed by lipase manifest substantial activity.The subsequent screening for best carbon,nitrogen,and inducer was performed using the Placket-Burman design(PBD).The statistically significant variables were further examined for their optimum level using Box-Behnken design(BBD).The lipase production was optimized(26.04 IU/ml)under the ideal molasses(2.5%),peptone(2%),and salt(0.1%CaCO_(3),0.1%(NH_(4))2SO_(4),and 0.1%MgSO_(4).7H_(2)O).Both models revealed impeccable predictions;however,more interestingly,it was evaluated that ANN outperforms the RSM regarding data fitting and estimation capabilities.展开更多
基金supported by National Science Foundation of China(No.81502961)National Key Project of Science and Technology(No.2012ZX09103-101-030)+2 种基金the"333"Project of Jiangsu Province(No.BRA2015321)the Priority Academic Program Development of Jiangsu Higher Education Institutionsthe Project of University Collaborative Innovation Center of Jiangsu Province(Biological Medicine Center)
文摘Nocathiacin I, a glycosylated thiopeptide antibiotic, displays excellent antibacterial activities against multidrug resistant bacterial pathogens. Previously, a novel nocathiacin I formulation for intravenous administration has been successfully developed and its aqueous solubility is greatly enhanced for clinical application. The purpose of the present study was to increase the fermentation titer of nocathiacin I and reduce or eliminate analogous impurities by screening the medium ingredients using response surface methodology. After a sysmatic optimization, a water-soluble medium containing quality-controllable components was developed and validated, resulting in an increase in the production of nocathiacin I from 150 to 405.8 mg·L-1 at 150-L scale. Meanwhile, the analogous impurities existed in reported processes were greatly reduced or eliminated. Using optimized medium for fermentation, nocathiacin I with pharmaceutically acceptable quality was easily obtained with a recovery of 67%. In conclusion, the results from the present study offer a practical and efficient fermentation process for the production of nocathiacin I as a therapeutic agent.
文摘The goal of this study was to use statistical optimization to change the nutritional and environmental conditions so that Streptomyces baarensis MH-133 could make more active metabolites.Twelve trials were used to screen for critical variables influencing productivity using the Placket-Burman Design method.S.baarensis MH-133 is significantly influenced by elicitation,yeast extract,inoculum size,and incubation period in terms of antibacterial activity.A total of 27 experimental trials with various combinations of these factors were used to carry out the response surface technique using the Box-Behnken design.The analyses revealed that the model was highly significant(p<0.001),with a lack-of-fit of 0.212 and a coefficient determination(R2)of 0.9224.Additionally,the model predicted that the response as inhibition zone diameter would reach a value of 27 mm.Under optimal conditions,S.baarensis MH-133 produced 18.0 g of crude extract to each 35L and was purified with column chromatography.The active fraction exhibiting antibacterial activity was characterized using spectroscopic analysis.The MIC and MBC values varied between 37.5 and 300μg/ml and 75 and 300μg/ml,respectively.In conclusion,the biostatistical optimization of the active fraction critical variables,including environmental and nutritional conditions,enhances the production of bioactive molecules by Streptomyces species.
文摘Response surface methodology(RSM)and artificial neural networks(ANN)are considered the most efficient way for opti-mization and modeling studies to design and develop various biosimilars.The primary objective of this study was to create empirical modeling and optimization of media parameters for producing B.halotolerans VSH 09 lipase using RSM and ANN.One-factor-at-a-time(OFAT)analysis revealed that triacylglycerols hydrolyzed by lipase manifest substantial activity.The subsequent screening for best carbon,nitrogen,and inducer was performed using the Placket-Burman design(PBD).The statistically significant variables were further examined for their optimum level using Box-Behnken design(BBD).The lipase production was optimized(26.04 IU/ml)under the ideal molasses(2.5%),peptone(2%),and salt(0.1%CaCO_(3),0.1%(NH_(4))2SO_(4),and 0.1%MgSO_(4).7H_(2)O).Both models revealed impeccable predictions;however,more interestingly,it was evaluated that ANN outperforms the RSM regarding data fitting and estimation capabilities.
