The invention provides methods for improving efficiency of fermentation by arginine supplementation, and genetically modified bacterium for use therefor. More particularly the invention provides methods for (i) increasing the production ATP intensive products with arginine supplementation, (ii) increasing utilization of arginine by a C1-fixing bacterium; and (iii) providing C1-fixing bacterium with optimized arginine de-aminase pathways.

Provided are chimeric arginine deiminases, including pegylated chimeric arginine deiminases, and related compositions and methods of use thereof, including methods of treating cancer.

The invention relates to compositions comprising arginine deiminase and their use in a method of reducing aggregation of disordered protein in a subject.

The present invention relates to the use of proteins, enzymes and probiotics to create a wholistic system that prevents negative effects of protein indigestion on gut microbiota and improves diversity and count of gut microbiota, thereby promoting microflora balance. The invention, in one or more embodiments, increases the bioavailability of postbiotics that regulate health, including, skin health, stress, anxiety and depression, physical endurance, healthy aging, inflammation and cardiac health. The invention, in one or more embodiments, also increases the bioavailability of essential, non-essential and branched amino acids.

Peptides related to certain portions of the arginine deiminase enzyme from the bacterium Streptococcus cristatus are provided that disrupt the formation and composition of biofilms containing the oral pathogen Porphyromonas gingivalis, and also modulate the virulence of P. gingivalis. Pharmaceutical compositions containing such peptides and method of using the same are disclosed.

A genetically engineered arginine deiminase reconstructed by site-directed mutagenesis belongs to the technical field of genetic engineering technology. Its amino acid sequence is shown as SEQ ID No. 1. In the amino acid sequence of the arginine deiminase reconstructed by site-directed mutagenesis, glycine at position 264 is mutated to proline, compared to an amino acid sequence of native arginine deiminase. Compared with wild type enzyme, the effective pH range effect of the mutated arginine deiminase according to the present invention is broadened to a certain extent, and especially a good enzyme activity is achieved at physiological pH 7.4. With the broadening of the effective pH effect range, the mutant enzyme still has higher stability under the condition of pH 5.5-7.5. Therefore, the problem that the arginine deiminase generally is low in enzymatic activity and short in half-life in vivo under physiological conditions in clinical application for tumor therapy is solved, and a good condition for using the enzyme and an encoding gene thereof for clinical treatment is created.

The present invention provides a pharmaceutical composition containing albumin-binding arginine deiminase fusion protein (AAD) for treating cancer or other arginine-dependent diseases. The AAD fission protein can be purified from both soluble and insoluble fractions of crude proteins, it binds to human serum albumin (HSA) and has its high activity with longer half life for efficient depletion of arginine in cancer cells. The specific activities of wild-type ADI and AAD in the present invention are 8.4 and 9.2 U/mg (at physiological pH 7.4), respectively. The AAD used in the present invention can be used in the treatment of various cancers (e.g. pancreatic cancer, leukemia, head and neck cancer, colorectal cancer, lung cancer, breast cancer, liver cancer, nasopharyngeal cancer, esophageal cancer, prostate cancer, stomach cancer & brain cancer) and curing arginine-dependent diseases. The composition can be used alone or in combination with at least one chemotherapeutic agent to give a synergistic effect on cancer treatment and/or inhibiting metastasis.

Disclosed is a method for producing L-citrulline using recombinant Corynebacterium crenatum cells as whole-cell biocatalysts. The present invention provides a recombinant C. crenatum that expresses an exogenous arginine deiminase gene from Lactobacillus brevis. The recombinant C. crenatum SDNN403 is used as biocatalysts for converting L-arginine to produce L-citrulline. Using the method of the invention, the concentration of L-citrulline reached 301.4 g/L after a 48 hr conversion reaction, and the molar conversion rate reached 99.9%.

Provided are lyophilized formulations comprising pegylated arginine deiminase (ADI-PEG) and related reconstituted liquid compositions and methods of using the compositions for arginine depletion therapies, including for the treatment of various cancers.

Provided are conjugates of an arginine deiminase (ADI) and a Tumor Necrosis Factor (TNF) superfamily ligand, and related compositions and methods of use thereof. Also provided are conjugates of a hexameric polypeptide and a trimeric polypeptide, conjugates of a first and second trimeric polypeptide, and related compositions and methods of use thereof.