The present invention relates to a composition for producing a fermented milk product comprising (i) at least one Streptococcus thermophilus (St) strain, wherein the St strain is galactose-fermenting, wherein the strain carries a mutation in the DNA sequence of the glcK gene encoding a glucokinase protein, wherein the mutation inactivates the glucokinase protein or has a negative effect on expression of the gene, and (ii) at least one Lactobacillus delbrueckii subsp. bulgaricus (Lb) strain, wherein the Lb strain is lactose-deficient and capable of metabolizing a non-lactose carbohydrate.

The present disclosure relates to a composition for producing tagatose, comprising fructose-6-phosphate-4-epimerase, and a method of producing tagatose using the same.

Recombinant strains are obtained for the production of allulose, allose, and allitol by regulating intracellular glucose metabolism, reducing the enzyme activity of fructose 6-phosphate kinase, and enhancing the enzyme activities of glucokinase and glucose-6-phosphate isomerase, allulose 6-phosphate 3-epimerase, allulose 6-phosphate phosphatase, fructose permease and fructokinase, and optionally enhancing the enzyme activities of ribose 5-phosphate isomerase, allose 6-phosphate phosphatase, ribitol dehydrogenase, glycerol permease, glycerol dehydrogenase, and dihydroxyacetone kinase. A method for producing allulose and allose is an extracellular multienzyme cascade method. Multienzyme cascade catalysis and fermentation are coupled to improve the conversion rate of starch sugar or sucrose to the synthesized allulose.

The present invention in various aspects and embodiments provides engineered bacterial strains having a modified genome that provides advantages in maintenance and biosynthetic processes when cultured at large scale. The present invention further provides methods for large-scale fermentation using the bacterial strains. In various embodiments, the strain engineering yields a reduction in cellular responses to micro-environmental stimuli imposed in large scale bioreactors.

The invention relates to a viral expression construct and related viral vector and composition and to their use wherein the construct and vector comprise elements a) and b): a) a nucleotide sequence encoding an insulin operably linked to a first promoter, b) a nucleotide sequence encoding a glucokinase operably linked to a second promoter and the viral expression construct and related viral vector comprise at least one of elements c), d) and e): c) the first and the second promoters are positioned in reverse orientation within the expression construct, d) the first and the second promoters are positioned in reverse orientation within the expression construct and are located adjacent to each other and e) the first promoter is a CMV promoter, preferably a mini CMV promoter.

The invention relates to double stranded ribonucleic acid (dsRNA) compositions targeting a glucokinase (GCK) gene, as well as methods of inhibiting expression of a glucokinase (GCK) gene, and methods of treating subjects having a glycogen storage disease (GSD), e.g., type Ia GSD.

The present invention relates generally to a population of cells genetically modified to produce insulin in a glucose responsive manner and uses thereof. More particularly, the present invention relates to a population of cells genetically modified to produce insulin in response to physiologically relevant levels of glucose and uses thereof. The cells of the present invention are useful in a wide variety of applications, in particular in the context of therapeutic and prophylactic regimes directed to the treatment of diabetes and/or the amelioration of symptoms associated with diabetes, based on the transplantation of the cells of the present invention into mammals requiring treatment. Also facilitated is the design of in vitro based screening systems for testing the therapeutic effectiveness and/or toxicity of potential adjunctive treatment regimes.

The invention is directed to a lactose-positive, galactose-negative, Streptococcus thermophilus strain releasing glucose during milk fermentation. This Streptococcus thermophilus strain carries mutation in the glcK gene, in the ccpA gene, in the lacZ gene and/or in the ptsH gene, and optionally in one or more genes, in particular one gene, encoding a protein of the mannose-glucose-specific PTS. The invention also concerns a composition comprising at least one, lactose-positive, galactose-negative, Streptococcus thermophilus strain of the invention, and the use of this strain or composition to manufacture a fermented dairy product.

The invention relates to double stranded ribonucleic acid (dsRNA) compositions targeting a glucokinase (GCK) gene, as well as methods of inhibiting expression of a glucokinase (GCK) gene, and methods of treating subjects having a glycogen storage disease (GSD), e.g., type Ia GSD.

The present disclosure relates to tagatose-6-phosphate phosphatase consisting of an amino acid sequence of SEQ ID NO: 1, a nucleic acid encoding the tagatose-6-phosphate phosphatase, and a transformant comprising the nucleic acid. Additionally, the present disclosure relates to a composition for producing tagatose, which comprises the tagatose-6-phosphate phosphatase of the present disclosure, and a method for producing tagatose using the tagatose-6-phosphate phosphatase of the present disclosure.