The present invention relates to Actinomycetales strains for the improved formation of acarbose. Provided are Actinomycetales strains which are engineered to overexpress dTDP-D-glucose-4,6-dehydratase (AcbB) and/or uridyltransferase (GtaB). Also provided are Actinomycetales strains which are engineered to have a reduced or absent expression of the small carbohydrate binding protein (Cgt) and/or a reduced or absent expression of genes which are essential for carotenoid synthesis. Also provided are tools, methods and means to generate these strains.

The present invention relates to Actinomycetales strains for the improved formation of acarbose. Provided are Actinomycetales strains which are engineered to overexpress dTDP-D-glucose-4,6-dehydratase (AcbB) and/or uridyltransferase (GtaB). Also provided are Actinomycetales strains which are engineered to have a reduced or absent expression of the small carbohydrate binding protein (Cgt) and/or a reduced or absent expression of genes which are essential for carotenoid synthesis. Also provided are tools, methods and means to generate these strains.

The present disclosure includes refactored thaxtomin biosynthetic gene clusters including thaxtomin modules including one or more thaxtomin genes such that the expression of the refactored thaxtomin biosynthetic gene cluster produces at least one thaxtomin compound in the absence of thaxtomin-inducing conditions. Also included are genetically engineered Streptomyces bacterium from a non-pathogenic Streptomyces strain comprising an exogenous, refactored thaxtomin biosynthetic gene cluster of the present disclosure, such that the expression of the refactored thaxtomin biosynthetic gene cluster provides the genetically engineered Streptomyces bacterium with the ability to produce at least one thaxtomin compound in the absence of thaxtomin-inducing conditions. The present disclosure also includes methods of producing thaxtomin compounds, analogs, or intermediate with the refactored thaxtomin biosynthetic gene clusters and genetically engineered bacteria of the present disclosure.

The present disclosure includes refactored thaxtomin biosynthetic gene clusters including thaxtomin modules including one or more thaxtomin genes such that the expression of the refactored thaxtomin biosynthetic gene cluster produces at least one thaxtomin compound in the absence of thaxtomin-inducing conditions. Also included are genetically engineered Streptomyces bacterium from a non-pathogenic Streptomyces strain comprising an exogenous, refactored thaxtomin biosynthetic gene cluster of the present disclosure, such that the expression of the refactored thaxtomin biosynthetic gene cluster provides the genetically engineered Streptomyces bacterium with the ability to produce at least one thaxtomin compound in the absence of thaxtomin-inducing conditions. The present disclosure also includes methods of producing thaxtomin compounds, analogs, or intermediate with the refactored thaxtomin biosynthetic gene clusters and genetically engineered bacteria of the present disclosure.

The present disclosure provides an attenuated Nocardia seriolae and its construction method and use thereof, which belongs to the technical field of genetic engineering. In the present disclosure, part or all of the glutamate endopeptidase homologue (GluNS) gene sequence of wild-type Nocardia seriolae is knocked out by means of genetic engineering to construct an attenuated strain with the characterized of good protection to the host. The attenuated strain may not only effectively reduce the pathogenicity of the bacteria, but also retain good immunogenicity. At the same time, the attenuated Nocardia seriolae constructed in the present disclosure may also have the characteristics of high genetic stability and may be used as a vaccine candidate strain for the preparation of a vaccine or other biological products for preventing and treating Nocardiosis.

The present disclosure provides an attenuated Nocardia seriolae and its construction method and use thereof, which belongs to the technical field of genetic engineering. In the present disclosure, part or all of the glutamate endopeptidase homologue (GluNS) gene sequence of wild-type Nocardia seriolae is knocked out by means of genetic engineering to construct an attenuated strain with the characterized of good protection to the host. The attenuated strain may not only effectively reduce the pathogenicity of the bacteria, but also retain good immunogenicity. At the same time, the attenuated Nocardia seriolae constructed in the present disclosure may also have the characteristics of high genetic stability and may be used as a vaccine candidate strain for the preparation of a vaccine or other biological products for preventing and treating Nocardiosis.

The invention relates to a metabolic enzyme-disrupted aerobic strain and a method for culturing the strain. The present invention provides, for example, a culture comprising a culture medium that has been cultured under an aerobic condition, wherein the culture medium contains an aerobe, wherein the aerobe has a disrupted gene encoding a metabolic enzyme of glycolysis selected from the group consisting of the metabolic enzymes of glycolysis except hexokinase, thereby suppressing metabolism from a carbon source (e.g., glucose) to the TCA cycle in the aerobe.

The present invention is directed to a method for manufacturing an enzyme preparation, comprising at least one recombinant Actinoallomurus endopeptidase with glutenase activity, at high yields and suitable for human use. The invention is further directed to a recombinant expression vector for expressing the recombinant endopeptidase(s) of interest, and to a S. lividans host cell comprising said vector. Moreover, the present invention is directed the enzyme preparation obtained by said method, to formulations of the same and to clinical uses thereof.

The present invention is directed to a method for manufacturing an enzyme preparation, comprising at least one recombinant Actinoallomurus endopeptidase with glutenase activity, at high yields and suitable for human use. The invention is further directed to a recombinant expression vector for expressing the recombinant endopeptidase(s) of interest, and to a S. lividans host cell comprising said vector. Moreover, the present invention is directed the enzyme preparation obtained by said method, to formulations of the same and to clinical uses thereof.

The invention relates to C. acnes strains carrying DNA vectors for the production of recombinant C. acnes phages. The invention encompasses a C. acnes producer cell carrying DNA vectors, with a template for recombination with C. acnes phage genome leading to the insertion of a gene of interest, for the production of recombinant phages that can lead to the transgene expression into C. acnes infected by the recombinant phage. The invention encompasses, C. acnes strains containing these vectors, C. acnes recombinant phages and methods of using these recombinant phages.