The present disclosure describes the engineering of microbial cells for fermentative production of histamine and provides novel engineered microbial cells and cultures, as well as related histamine production methods.

The present invention provides a mutated histidine decarboxylase suitable for a practical use. Specifically, the present invention provides a mutated histidine decarboxylase having at least one amino acid residue mutated as compared to a wild-type histidine decarboxylase, and having higher histidine decarboxylase activity and/or stability than the wild-type histidine decarboxylase, and also a use thereof. The mutated histidine decarboxylase has Motifs (1) to (6), and an amino acid residue in at least one motif thereof can be mutated. The mutated histidine decarboxylase can also have a mutation of at least one amino acid residue in an amino acid sequence designated by SEQ ID NO: 3 and in a homologous sequence thereto.

The present invention provides a mutated histidine decarboxylase suitable for a practical use. Specifically, the present invention provides a mutated histidine decarboxylase having at least one amino acid residue mutated as compared to a wild-type histidine decarboxylase, and having higher histidine decarboxylase activity and/or stability than the wild-type histidine decarboxylase, and also a use thereof. The mutated histidine decarboxylase has Motifs (1) to (6), and an amino acid residue in at least one motif thereof can be mutated. The mutated histidine decarboxylase can also have a mutation of at least one amino acid residue in an amino acid sequence designated by SEQ ID NO: 3 and in a homologous sequence thereto.

The present invention relates to nucleic acid molecules from regions of Enterococcus spp. genomes which are associated with the production of dopamine The invention also relates to proteins encoded by such nucleic acid molecules as well as nucleic acid markers which are associated with high dopamine production. Moreover, the invention relates to uses of such molecules, including, but not limited to, transforming or transfecting cells or organisms with constructs containing the nucleic acid molecules to create cells or organisms with enhanced dopamine production. The present invention is also directed to kits for identifying bacteria which may be capable of producing dopamine based on the detection of the nucleic acid molecules.

The present invention relates to a combination therapy for the treatment of cancer, particularly to combinations of oligo(2-(2-ethoxy)ethoxy ethyl guanidinium chloride), poly(hexamethylendiamine guanidiniumchloride), polyetheramines, triethyleneglycol diamine, enzymes, PGPR, amino acids, antioxidants like humic acids and some natural products like phytotherapeutic plant extracts. The combination therapy of the present invention shows enhanced anti-cancerous therapeutic effects compared to the effect of each of the components administered alone. In some embodiments, the combination therapy provide for a synergistic anti-cancer effect. A liposomal drug composition comprising; A dimeric or polymeric guanidine derivative or polyetheramines, triethyleneglycol diamine, enzymes, PGPR, amino acids, antioxidants like humic acids and some natural products like phytotherapeutic plant extracts a pharmaceutically acceptable salt thereof as drug substance, and a lipid modified by polyethylene glycole (PEG).

The present disclosure describes the engineering of microbial cells for fermentative production of histamine and provides novel engineered microbial cells and cultures, as well as related histamine production methods.

The present invention provides a PEG-ACS/M-siRNA nanocomposite application, and method for reducing the histamine content during fishmeal storage thereof. A small interfering ribonucleic acid (siRNA) is designed and prepared according to a histidine decarboxylase gene of Morganella morganii (Morganella morganii subsp. morganii KT), and the histidine decarboxylase gene has a sequence of SEQ ID No: 1. A PEG-ACS/M-siRNA nanocomposite is prepared by using a PEGylated arginine-modified chitosan as a carrier. A PEG-ACS/M-siRNA nanocomposite is added to fishmeal in a certain ratio. The method for reducing the histamine content during fishmeal storage has a significant inhibitory effect on the histamine content during fishmeal storage, and can reduce the histamine content in fishmeal by 49%-53%, which has great significance for the control of biogenic amines in fishmeal in the feed industry.

The present invention provides a PEG-ACS/M-siRNA nanocomposite application, and method for reducing the histamine content during fishmeal storage thereof. A small interfering ribonucleic acid (siRNA) is designed and prepared according to a histidine decarboxylase gene of Morganella morganii (Morganella morganii subsp. morganii KT), and the histidine decarboxylase gene has a sequence of SEQ ID No: 1. A PEG-ACS/M-siRNA nanocomposite is prepared by using a PEGylated arginine-modified chitosan as a carrier. A PEG-ACS/M-siRNA nanocomposite is added to fishmeal in a certain ratio. The method for reducing the histamine content during fishmeal storage has a significant inhibitory effect on the histamine content during fishmeal storage, and can reduce the histamine content in fishmeal by 49%-53%, which has great significance for the control of biogenic amines in fishmeal in the feed industry.

The present invention provides a mutated histidine decarboxylase suitable for a practical use. Specifically, the present invention provides a mutated histidine decarboxylase having at least one amino acid residue mutated as compared to a wild-type histidine decarboxylase, and having higher histidine decarboxylase activity and/or stability than the wild-type histidine decarboxylase, and also a use thereof. The mutated histidine decarboxylase has Motifs (1) to (6), and an amino acid residue in at least one motif thereof can be mutated. The mutated histidine decarboxylase can also have a mutation of at least one amino acid residue in an amino acid sequence designated by SEQ ID NO: 3 and in a homologous sequence thereto.

The present disclosure describes the engineering of microbial cells for fermentative production of histamine and provides novel engineered microbial cells and cultures, as well as related histamine production methods.