Efficient synthesis of tyrosol from L-tyrosine via heterologous Ehrlich pathway in Escherichia coli

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.

Optimization of L(+)-Lactic Acid Fermentation Without Neutralisation of Rhizopus Oryzae Mutant RK02 by Low-Energy Ion 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.

Gut Microbiota Brings a Novel Way to Illuminate Mechanisms of Natural Products in vivo

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.