For the efficient conversion of L-tyrosine(L-Tyr)to tyrosol,which is an aromatic compound widely used in the pharmaceutical and chemical industries,a novel four-enzyme cascade pathway based on the Ehrlich pathway of S...For the efficient conversion of L-tyrosine(L-Tyr)to tyrosol,which is an aromatic compound widely used in the pharmaceutical and chemical industries,a novel four-enzyme cascade pathway based on the Ehrlich pathway of Saccharomyces cerevisiae was designed and reconstructed in Escherichia coli.Then,the expression levels of the relevant enzymes were coordinated using a modular approach and gene duplication after the identification of the pyruvate decarboxylase from Candida tropicalis(CtPDC)as the rate-limiting enzymatic step.In situ product removal(ISPR)strategy with XAD4 resins was explored to avoid product inhibition and further improve tyrosol yield.As a result,the titer and conversion rate of tyrosol obtained were 35.7 g·L^(-1) and 93.6%,respectively,in a 3-L bioreactor.Results presented here provide a potential enzymatic process for industrial production of tyrosol from cheap amino acids.展开更多
In order to get an industrial strain which can yield a high concentration of lactic acid for ISPR (in situ product removal), the original strain Rhizopus oryzae RE3303 was mutated by low-energy ion beam implantation...In order to get an industrial strain which can yield a high concentration of lactic acid for ISPR (in situ product removal), the original strain Rhizopus oryzae RE3303 was mutated by low-energy ion beam implantation. A mutant RK02 was screened, and the factors such as the substrate concentration, nitrogen source concentration, inoculum size, seed age, aeration and temperature that affect the production of lactic acid were studied in detail. Under optimal con- ditions, the maximum concentration of L(+)-lactic acid reached 34.85 g/L after 30 h shake-flask cultivation without adding any neutralisation (5% Glucose added), which was a 146% increase in lactic acid production after ion implantation compared with the original strain. It was also shown that RK02 can be used in ISPR to reduce the number of times of separation.展开更多
Poor bioavailability and undefined major/direct targets are two major obstacles for herbal medicines and natural products(NPs) to elucidate their precise mechanisms in vivo. Gut microbiota is an important bridge bet...Poor bioavailability and undefined major/direct targets are two major obstacles for herbal medicines and natural products(NPs) to elucidate their precise mechanisms in vivo. Gut microbiota is an important bridge between eukayotic body and environment, which can interact with a majority of medicines with poor bioavailability and mediate their in vivo pharmacological activities. There are two main modes through which gut microbiota may mediate the pharmacological effects of NPs. First, gut microbiota catabolizes the NPs in herbal medicines into secondary metabolites with higher bioavialability and/or higher activity, facilitating the NPs enter circulation and exert beneficial impact at the pathological spot. Second, herbal medicines and NPs can favorably shift the compositional structure of gut microbiota, thereby performing remote functions to diseased organs/tissues via the systemic impaction of gut microbiota. In this review, the potential pathways were summarized through which gut microbes facilitate the pharmacological functions of herbal medicines and NPs and highlight the significance of gut microbiota in clarifying the in vivo mechanisms of herbal medicines and NPs.展开更多
基金financially supported by the Fundamental Research Funds for the Central Universities (JUSRP21915)National Natural Science Foundation of China (22008089, 21878126)+2 种基金Provincial Natural Science Foundation of Jiangsu Province(BK20200622)the key technologies Research&Development Program of Jiangsu Province (BE2018623)the National First-Class Discipline Program of Light Industry Technology and Engineering(LITE2018-20)
文摘For the efficient conversion of L-tyrosine(L-Tyr)to tyrosol,which is an aromatic compound widely used in the pharmaceutical and chemical industries,a novel four-enzyme cascade pathway based on the Ehrlich pathway of Saccharomyces cerevisiae was designed and reconstructed in Escherichia coli.Then,the expression levels of the relevant enzymes were coordinated using a modular approach and gene duplication after the identification of the pyruvate decarboxylase from Candida tropicalis(CtPDC)as the rate-limiting enzymatic step.In situ product removal(ISPR)strategy with XAD4 resins was explored to avoid product inhibition and further improve tyrosol yield.As a result,the titer and conversion rate of tyrosol obtained were 35.7 g·L^(-1) and 93.6%,respectively,in a 3-L bioreactor.Results presented here provide a potential enzymatic process for industrial production of tyrosol from cheap amino acids.
基金the Eleventh Five-Year Planthe National 863 Program(No.2006AA020101)
文摘In order to get an industrial strain which can yield a high concentration of lactic acid for ISPR (in situ product removal), the original strain Rhizopus oryzae RE3303 was mutated by low-energy ion beam implantation. A mutant RK02 was screened, and the factors such as the substrate concentration, nitrogen source concentration, inoculum size, seed age, aeration and temperature that affect the production of lactic acid were studied in detail. Under optimal con- ditions, the maximum concentration of L(+)-lactic acid reached 34.85 g/L after 30 h shake-flask cultivation without adding any neutralisation (5% Glucose added), which was a 146% increase in lactic acid production after ion implantation compared with the original strain. It was also shown that RK02 can be used in ISPR to reduce the number of times of separation.
基金National Natural Science Foundation of China(No.81673663)CAMS Innovation Fund for Medical Sciences(CIFMS 2016-I2M-3-015)
文摘Poor bioavailability and undefined major/direct targets are two major obstacles for herbal medicines and natural products(NPs) to elucidate their precise mechanisms in vivo. Gut microbiota is an important bridge between eukayotic body and environment, which can interact with a majority of medicines with poor bioavailability and mediate their in vivo pharmacological activities. There are two main modes through which gut microbiota may mediate the pharmacological effects of NPs. First, gut microbiota catabolizes the NPs in herbal medicines into secondary metabolites with higher bioavialability and/or higher activity, facilitating the NPs enter circulation and exert beneficial impact at the pathological spot. Second, herbal medicines and NPs can favorably shift the compositional structure of gut microbiota, thereby performing remote functions to diseased organs/tissues via the systemic impaction of gut microbiota. In this review, the potential pathways were summarized through which gut microbes facilitate the pharmacological functions of herbal medicines and NPs and highlight the significance of gut microbiota in clarifying the in vivo mechanisms of herbal medicines and NPs.