Improved yields of melanin are obtained by incubating, in an optimized media with a disodium tyrosine substrate, a culture of Vibrio natriegens expressing a heterologous tyrosinase gene at a temperature of about 30 C.

The present invention relates to a plasmid-based CTX phage replication system and Vibrio cholerae strain that can be infected by CTX phage and can be used for cholera toxin production. More particularly, the present invention provides a Vibrio cholera variant strain, which expresses a toxT protein in which tyrosine at position 139 is substituted by phenylalanine through the point mutation of a toxT gene using a plasmid-based CTX phage replication system, and is used as a receptor strain which can improve CTX phage infection efficiency and allows a plurality of CTX prophages to simultaneously infect the strain and to be inserted into the chromosome thereof, which the consequent provision of the effect of increasing the production yield of a cholera toxin.

The invention provides engineered Vibrio sp. organisms that comprise a genetic modification to either or both of the lpxL and/or lpxM genes. The organisms score substantially lower in an in vitro endotoxin assay versus the unmodified or wild type organism. The organisms preserve substantially the growth rate of the corresponding unmodified organisms. The organisms can also have an exogenous nucleic acid cloned in the organism, or an exogenous nucleic acid encoding a protein, polypeptide, or peptide expressed by the organism, and optionally secreted from the organism.

The invention provides novel compounds of formula (I) and their pharmaceutically acceptable salts, metabolites, isomers (e.g. stereoisomers) and prodrugs. Such compounds are effective in the treatment of infections caused by Gram-negative bacteria such as Acinetobacter baumannii. In formula (I), X is O, NR (where R is either H or C.sub.1-3 alkyl, e.g. CH.sub.3), or CH.sub.2; R.sup.3 is H, F, CI, Br, I, or CH.sub.3; R.sup.4 is H, or OH; R.sup.5 and R.sup.6 are independently selected from H and OH, or R.sup.5 and R.sup.6 together are ?O; R.sup.7 is H, F, CI, Br, I, or CH.sub.3; R.sup.8 is H, OH, or OC(O)NR.sub.2 (where each R is independently H or C.sub.1-3 alkyl, e.g. CH.sub.3), preferably R.sup.8 is H, OH or OC(O)NH.sub.2; R.sup.9 is a 5- or 6-membered, saturated or unsaturated, carbocyclic ring optionally substituted by one or more substituents, or R.sup.9 is an optionally substituted straight-chained or branched C.sub.1-6 alkyl group (e.g. C.sub.1-3 alkyl group); R.sup.10 is a straight-chained or branched C.sub.1-8 alkyl group (e.g. C.sub.1-6 alkyl group), a C.sub.4-6 cycloalkyl group, or an optionally substituted aryl or heteroaryl group; and each --- independently represents an optional bond (i.e. each of C.sub.2-C.sub.3, C.sub.4-C.sub.5, C.sub.6-C.sub.7, C.sub.8-C.sub.9, C.sub.10-C.sub.11 and C.sub.18-C.sub.19 are independently either CC (single) or C?C (double) bonds).

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A method of constitutively expressing a bacterial dinucleotide cyclase in a mammalian cell is provided. The method comprises transfecting the mammalian cell with a transgene encoding the bacterial dinucleotide cyclase and subjecting the mammalian cell to suitable growth conditions. In an embodiment, the bacterial dinucleotide cyclase is expressed in a tumour or cancer cell and is useful to treat cancer.

A process is disclosed for production of a polyhydroxyalkanoate that includes depolymerization of a post-consumer polyhydroxyalkanoate and utilization of the hydroxyalkanoate monomer thus produced as a carbon source for a microorganism capable of production of a polyhydroxyalkanoate. Methods can be utilized for true cyclic use of polyhydroxyalkanoates including polyhydroxybutyrates. Various aspects are described including simultaneous depolymerization and polymer production, utilization of purified de-polymerase enzymes and/or microorganisms that express a depolymerase in conjunction with a microorganism that produces polymer, utilization of microorganisms that produce both a depolymerase and a new polymer, and utilization of genetically modified organisms to produce natural or modified depolymerase enzymes.

Bacterial strains are provided having at least one enhanced mechanism to sequester, bind, precipitate, chemically oxidize or reduce copper ions or other toxic divalent transition metals. The bacteria may also have optional copper resistance mechanisms. The bacteria reduce the amount of available copper to tissues, which may be cancerous tissues, and reduce tumor growth, angiogenesis and/or metastasis, or tissues subject to excess copper due to host defects in copper metabolism. The bacteria are useful for treatment of neoplastic diseases including solid tumors and lymphomas, as well as Wilson's Disease, Menke's Disease, and possible Alzheimer's Disease, Parkinson's Disease, and Creutzfeld-Jakob Disease.

The present disclosure provides compositions comprising recombinant bacterial spores. The present disclosure is also directed to vaccine based compositions, which include recombinant bacterial spores that express CTB and a peanut protein(s) on their surfaces. This disclosure also provides methods for administering these compositions as a treatment or prevention of peanut allergy.

The present disclosure provides furin-cleavable delivery constructs that include a transcytosing element that is derived from a mono-ADP-ribosyl transferase and a heterologous cargo that is coupled to the carrier. The carrier is capable of facilitating transport of the heterologous cargo across an epithelial cell via transcytosis. The heterologous cargo may be released from a remaining portion of the delivery construct upon cleavage by a furin protease. The constructs may be used to facilitate delivery of a cargo to a basolateral side of an epithelial membrane.

A process is disclosed for production of a polyhydroxyalkanoate that includes depolymerization of a post-consumer polyhydroxyalkanoate and utilization of the hydroxyalkanoate monomer thus produced as a carbon source for a microorganism capable of production of a polyhydroxyalkanoate. Methods can be utilized for true cyclic use of polyhydroxyalkanoates including polyhydroxybutyrates. Various aspects are described including simultaneous depolymerization and polymer production, utilization of purified depolymerase enzymes and/or microorganisms that express a depolymerase in conjunction with a microorganism that produces polymer, utilization of microorganisms that produce both a depolymerase and a new polymer, and utilization of genetically modified organisms to produce natural or modified depolymerase enzymes.