Polypeptide scaffolds comprising enzymatic proteins are provided. The enzymatic polypeptide scaffolds comprise heterologous enzymes to form a heterologous metabolic pathway, and can be targeted to a substrate through a surface anchoring domain. The enzymatic polypeptide scaffolds leverage the high specificity and affinity protein/protein interaction between the cohesins and dockerins of microorganismal cellulosomes to form custom enzymatic arrays.

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.

Described are composition and methods relate to reducing the redox imbalance in anaerobically growing yeast with attenuated glycerol production by re-engineering the pathway for Ac-CoA biosynthesis.

To specify a molecule associated with the onset of gout so as to provide a method for evaluating a diathesis of uric acid-related diseases and a diathesis of inflammation-related diseases, an evaluation kit for carrying out the method, an inspection object, and a drug, on the basis of the molecule specified above, for contributing to the early treatment and prevention of the uric acid-related diseases and inflammation-related diseases. The molecule includes any one protein and cDNA of CNIH2-PACS1, ALDH2, MYL2-CUX2, GCKR, MAP3K11, NPT4, ABCG2, HIST1H2BF/HIST1H4E, HIST1H2BE/HIST1H4D and FAM35A, or proteins of combination thereof with GLUT9, NPT1, URAT1, or NXRN2, and is capable of selectively inducing gout. A molecule includes protein and cDNA of an ABCG2 variant and is capable of selectively and ATP-dependently decreasing urate excretion.

A composition and method for converting alcohol to acetaldehyde and/or acetate and treat alcohol intoxication. The composition can include a therapeutically effective amount of an enzyme and a therapeutically effective amount of a co-factor. The enzymes can be alcohol dehydrogenase (ADH), a derivative of alcohol dehydrogenase, an analog of alcohol dehydrogenase or alcohol dehydrogenase in yeast crude extract. A second enzyme can be aldehyde dehydrogenase (ALDH), a derivative of aldehyde dehydrogenase, an analog of aldehyde dehydrogenase, mitochondrial aldehyde dehydrogenase (ALDH2), a derivative of mitochondrial aldehyde dehydrogenase, an analog of mitochondrial aldehyde dehydrogenase or aldehyde dehydrogenase in yeast crude extract. A co-factor can be utilized in the composition that increases a concentration of Nicotinamide Adenine Dinucleotide (NAD) or Nicotinamide Adenine Dinucleotide Phosphate (NADP). A sugar such as, but not limited to, fructose and a third enzyme sorbitol dehydrogenase (SDH) can be included in the composition.

Oligonucleotide conjugates are provided herein that inhibit or reduce expression of target genes in the CNS. Also provided are compositions including the same and uses thereof, particularly uses relating to treating diseases, disorders and/or conditions associated with target gene expression in the CNS.

The disclosure provides genetically engineered microorganisms and methods for improved biological production of ethylene glycol and precursors of ethylene glycol. The microorganism of the disclosure produces ethylene glycol or a precursor of ethylene glycol through one or more of 5,10-methylenetetrahydrofolate, oxaloacetate, citrate, malate, and glycine. The disclosure further provides compositions comprising ethylene glycol or polymers of ethylene glycol such as polyethylene terephthalate.

This disclosure describes enzymes from the type II (a discrete set of enzymes) fatty acid synthesis (FAS) pathway that can be used in combination with thiolases to operate a functional reversal of the -oxidation cycle. A combination of thiolases with one or more of 3-oxoacyl-[acyl-carrier-protein] reductase (FabG, others), 3-hydroxyacyl-[acp] dehydratase (FabA, FabZ, others), and enoyl-[acyl-carrier-protein] reductase (FabI, FabK, FabL, FabV, others) yields a functional reversal of the -oxidation cycle. If only one or two enzymes are used, the remaining enzymes will be traditional beta oxidation enzymes. Once this cycle is coupled with the appropriate priming and termination pathways, the production of carboxylic acids, alcohols, hydrocarbons, amines and their -, -, and -functionalized derivatives from renewable carbon sources can be achieved.

Provided herein are double-stranded nucleic acid inhibitor molecules having a sense strand with a stem loop structure and an antisense strand, where the stem portion of the stem loop structure contains one or more T.sub.m-increasing nucleotides. Also provided are methods and compositions for reducing target gene expression and methods and compositions for treating a disease of interest.

The present disclosure provides recombinant bacterial cells that have been engineered with genetic circuitry which allow the recombinant bacterial cells to sense a patient's internal environment and respond by turning an engineered metabolic pathway on or off. When turned on, the recombinant bacterial cells complete all of the steps in a metabolic pathway to achieve a therapeutic effect in a host subject. These recombinant bacterial cells are designed to drive therapeutic effects throughout the body of a host from a point of origin of the microbiome. Specifically, the present disclosure provides recombinant bacterial cells that comprise an amino acid catabolism enzyme for the treatment of diseases and disorders associated with amino acid metabolism, including cancer, in a subject. The disclosure further provides pharmaceutical compositions and methods of treating disorders associated with amino acid metabolism, such as cancer.