The present invention relates to an isolated chimeric molecule comprising a degradation domain including a eukaryotic U-box motif and a targeting domain capable of immunospecifically directing the degradation domain to a substrate where the targeting domain is heterologous to the degradation domain. A linker couples the degradation domain to the targeting domain. Also disclosed are compositions as well as methods of treating a disease, substrate silencing, screening agents for therapeutic efficacy against a disease, and methods of screening for disease biomarkers.

The present invention relates to a genetically engineered microorganism expressing (i) formate tetrahydrofolate (THF) ligase, methenyi-THF cyclohydrolase and methylene-THF dehydrogenase, (ii) the enzymes of the glycine cleavage system (GCS), (iii) serine deaminase and serine hydroxymethyltransferase (SHMT), (iv) an enzyme increasing the availability of NADPH, and (v) optionally formate dehydrogenase (FDH), and wherein the genetically engineered microorganism has been genetically engineered to express at least one of the enzymes of (i) to (v), wheren said enzyme is not expressed by the corresponding microorganism that has been used to prepare the genetically engineered microorganism, and wherein the enzymes of (i) to (v) are genomically expressed.

The present invention encompasses non-ribosomal peptides and non-ribosomal peptide synthetases, and the preparation and use thereof. Specifically encompassed are methods for preparing non-ribosomal peptide synthetases, methods for preparing non-ribosomal peptides from these enzymes, as well as polynucleotides used for producing these enzymes, libraries comprising these polynucleotides, and microbial strains comprising these polynucleotides.

The present invention provides recombinant bacterial cells comprising at least one heterologous gene encoding at least one oxalate catabolism enzyme. In another aspect, the recombinant bacterial cells further comprise at least one heterologous gene encoding an importer of oxalate. The invention further provides pharmaceutical compositions comprising the recombinant bacteria, and methods for treating disorders in which oxalate is detrimental, such as hyperoxaluria, using the pharmaceutical compositions of the invention.

The present disclosure provides methods and compositions for detecting and spatially locating analyte interactions and gene expression in a biological sample. For example, provided herein are methods of determining a location of at least one analyte in a biological sample using analyte-binding moieties, proximity ligation, and an array including capture probes.

Provided herein are compositions and methods to make and use engineered cells, for the purpose of increasing the cell density of a culture comprising metazoan cells and for the production of a cultured edible product.

Improved production of threonine from E. coli by fermentation is accomplished by attenuation but not elimination of the expression of either or both of the yafV gene encoding omega-amidase (a.k.a. 2-oxoglutaramate amidase). In certain embodiments the strain also has attenuated expression of the ilvA gene encoding threonine dehydratase (a.k.a threonine deaminase) in cases where there is attenuated express of the ilvA gene there is no need to express an exogenous cimA gene. In examples of both cases, attenuation is accomplished by engineering these genes to contain a weaker ribosome site. Further improvements in threonine production are made by expression of a heterologous pyruvate carboxylase gene exemplified by expression of the Corynebacterium glutamicum pyc gene under control of an E. coli promoter, to provide expression of pyruvate carboxylase that is not naturally expressed in E. coli. Still further improvement is accomplished by overexpression of the rhtC gene encoding the E. coli threonine transporter protein, exemplified by inserting a stronger ribosome binding site upstream of the open reading frame for the rhtC gene.

Methods of inserting genes into defined locations in the chromosomal DNA of cultured mammalian cell lines which are subject to gene amplification are disclosed. In particular, sequences of interest (e.g., genes encoding biotherapeutic proteins) are inserted proximal to selectable genes in amplifiable loci, and the transformed cells are subjected to selection to induce co-amplification of the selectable gene and the sequence of interest. The invention also relates to meganucleases, vectors and engineered cell lines necessary for performing the methods, to cell lines resulting from the application of the methods, and use of the cell lines to produce protein products of interest.

The invention provides non-naturally occurring microbial organisms containing a fatty alcohol, fatty aldehyde or fatty acid pathway, wherein the microbial organisms selectively produce a fatty alcohol, fatty aldehyde or fatty acid of a specified length. Also provided are non-naturally occurring microbial organisms having a fatty alcohol, fatty aldehyde or fatty acid pathway, wherein the microbial organisms further include an acetyl-CoA pathway. In some aspects, the microbial organisms of the invention have select gene disruptions or enzyme attenuations that increase production of fatty alcohols, fatty aldehydes or fatty acids. The invention additionally provides methods of using the above microbial organisms to produce a fatty alcohol, a fatty aldehyde or a fatty acid.

The invention is directed to methods involved in the production of flavonoids, anthocyanins and other organic compounds. The invention provides cells engineered for the production of flavonoids, anthocyanins and other organic compounds, where the engineered cells include one or more genetic modifications that increase flavonoid production by increasing metabolic flux to flavonoid precursors and/or reducing carbon losses resulting from the production of byproducts.