Dear Editor,Harnessing the power of the immune system via immune checkpoint inhibition has revolutionized the treatment paradigm of many malignancies,including hepatocellular carcinoma(HCC).1 Despite encouraging effic...Dear Editor,Harnessing the power of the immune system via immune checkpoint inhibition has revolutionized the treatment paradigm of many malignancies,including hepatocellular carcinoma(HCC).1 Despite encouraging efficacy seen with the immune checkpoint blockade(ICB)agents in a subset of patients with HCC,however,there remain a large number of HCC patients experience ICB resistance and failed to derive durable benefit from these agents.展开更多
(2R,3R)-BDO is an important bio-based four-carbon platform compound and widely used in chemical,food,pharmaceutical,fuel and aerospace fields.Serratia marcescens has been shown to be an effective strain for producing ...(2R,3R)-BDO is an important bio-based four-carbon platform compound and widely used in chemical,food,pharmaceutical,fuel and aerospace fields.Serratia marcescens has been shown to be an effective strain for producing BDO.However,there have been few reports on the metabolic engineering of this strain to efficiently produce(2R,3R)-BDO using xylose.In this study,the endogenous strong promoter was screened and modified,and combined with the screened RBS.(2R,3R)-BDO was successfully produced by combining the selected promoters and RBS with the overexpressed key enzymes(ALS,ALSD,BDH,GLF)of(2R,3R)-BDO production.The optimum fermentation temperature and pH were 37℃and 6.0,respectively,and the optimized yield reached 6.0 g/L.After batch fermentation,the(2R,3R)-BDO yield reached 36.6 g/L.This provided a good idea for efficient production of(2R,3R)-BDO from xylose.展开更多
Beyond its potential for biofuel production,Pseudomonas putida’s capability to metabolize lignin and other lignocellulosic materials earmarks it as a pivotal candidate for engineering to yield diverse value-added che...Beyond its potential for biofuel production,Pseudomonas putida’s capability to metabolize lignin and other lignocellulosic materials earmarks it as a pivotal candidate for engineering to yield diverse value-added chemicals,thereby challenging traditional petrochemical approaches.Recognizing the inherent environmental,economic,and societal advantages,ampli-fying role of P.putida in industrial applications becomes imperative.In this context,our study focused on characterizing a comprehensive set of promoters and ribosome binding site tailored for P.putida,spanning a broad spectrum of activities.By leveraging these genetic tools,we adeptly balanced the heterologous mevalonate(MVA)pathway flux within P.putida.As a culmination of our efforts,the optimal MVA-producing strains were identified,achieving a remarkable yield of 5 g/LMVA in a 5 L fed-batch fermenter,marking the highest reported yield in Pseudomonas to date.This research not only provides valuable genetic tools for future engineering studies with P.putida,but also accentuates P.putida’s potential in synthetic biology and its promise for sustainable chemical production.展开更多
基金This work was supported by the National Natural Science Foundation of China(81920108025,81874229,82072633,and 82122047)the Innovative Research Team of High-level Local Universities in Shanghai(SHSMU-ZLCX20211602)Shanghai Natural Science Foundation(22ZR1480900).
文摘Dear Editor,Harnessing the power of the immune system via immune checkpoint inhibition has revolutionized the treatment paradigm of many malignancies,including hepatocellular carcinoma(HCC).1 Despite encouraging efficacy seen with the immune checkpoint blockade(ICB)agents in a subset of patients with HCC,however,there remain a large number of HCC patients experience ICB resistance and failed to derive durable benefit from these agents.
文摘(2R,3R)-BDO is an important bio-based four-carbon platform compound and widely used in chemical,food,pharmaceutical,fuel and aerospace fields.Serratia marcescens has been shown to be an effective strain for producing BDO.However,there have been few reports on the metabolic engineering of this strain to efficiently produce(2R,3R)-BDO using xylose.In this study,the endogenous strong promoter was screened and modified,and combined with the screened RBS.(2R,3R)-BDO was successfully produced by combining the selected promoters and RBS with the overexpressed key enzymes(ALS,ALSD,BDH,GLF)of(2R,3R)-BDO production.The optimum fermentation temperature and pH were 37℃and 6.0,respectively,and the optimized yield reached 6.0 g/L.After batch fermentation,the(2R,3R)-BDO yield reached 36.6 g/L.This provided a good idea for efficient production of(2R,3R)-BDO from xylose.
文摘Beyond its potential for biofuel production,Pseudomonas putida’s capability to metabolize lignin and other lignocellulosic materials earmarks it as a pivotal candidate for engineering to yield diverse value-added chemicals,thereby challenging traditional petrochemical approaches.Recognizing the inherent environmental,economic,and societal advantages,ampli-fying role of P.putida in industrial applications becomes imperative.In this context,our study focused on characterizing a comprehensive set of promoters and ribosome binding site tailored for P.putida,spanning a broad spectrum of activities.By leveraging these genetic tools,we adeptly balanced the heterologous mevalonate(MVA)pathway flux within P.putida.As a culmination of our efforts,the optimal MVA-producing strains were identified,achieving a remarkable yield of 5 g/LMVA in a 5 L fed-batch fermenter,marking the highest reported yield in Pseudomonas to date.This research not only provides valuable genetic tools for future engineering studies with P.putida,but also accentuates P.putida’s potential in synthetic biology and its promise for sustainable chemical production.