Provided herein are genetically engineered microbes that include at least a portion of a carbon fixation pathway, and in one embodiment, use molecular hydrogen to drive carbon dioxide fixation. In one embodiment, the genetically engineered microbe is modified to convert acetyl CoA, molecular hydrogen, and carbon dioxide to 3-hydroxypropionate, 4-hydroxybutyrate, acetyl CoA, or the combination thereof at levels greater than a control microbe. Other products may also be produced. Also provided herein are cell free compositions that convert acetyl CoA, molecular hydrogen, and carbon dioxide to 3-hydroxypropionate, 4-hydroxybutyrate, acetyl CoA, or the combination thereof. Also provided herein are methods of using the genetically engineered microbes and the cell free compositions.

Polynucleotide expression cassettes comprising synthetic polynucleotides encoding human propionyl-CoA carboxylase alpha (synPCCA) are described herein. Related recombinant expression vectors, recombinant adeno-associated viruses (rAAVs), and compositions are also described. Also described are methods of treating a disease or condition mediated by propionyl-CoA carboxylase, comprising administering to a subject in need thereof a therapeutic amount of any of the polynucleotide expression cassettes, recombinant expression vectors, rAAVs, or compositions.

Provided herein are genetically engineered microbes that include at least a portion of a carbon fixation pathway, and in one embodiment, use molecular hydrogen to drive carbon dioxide fixation. In one embodiment, the genetically engineered microbe is modified to convert acetyl CoA, molecular hydrogen, and carbon dioxide to 3-hydroxypropionate, 4-hydroxybutyrate, acetyl CoA, or the combination thereof at levels greater than a control microbe. Other products may also be produced. Also provided herein are cell free compositions that convert acetyl CoA, molecular hydrogen, and carbon dioxide to 3-hydroxypropionate, 4-hydroxybutyrate, acetyl CoA, or the combination thereof. Also provided herein are methods of using the genetically engineered microbes and the cell free compositions.

Sedoheptulose, which is a saccharide falling within the categories of ketoses and heptuloses, is one of a small number of heptuloses occurring in nature. Provided are a method for producing sedoheptulose using a bacterium owing to the deletion or attenuation of a specific enzymatic function, a method for improving the productivity of sedoheptulose by the bacterium, and the bacterium.

This present disclosure provides adeno-associated viral vectors, recombinant adeno-associated virus (rAAV), and methods of their use in gene therapy for treating propionic acidemia (PA). Also provided are pharmaceutical compositions comprising a recombinant adeno-associated virus of the invention and a pharmaceutically acceptable carrier or excipient. These pharmaceutical (compositions may be useful in gene therapy for the treatment of PA caused by mutations in propionyl-CoA carboxylase -subunit (PCCA) or mutations in propionyl-CoA carboxylase -subunit (PCCB).

This present disclosure provides adeno-associated viral vectors, recombinant adeno-associated virus (rAAV), and methods of their use in gene therapy for treating propionic acidemia (PA). Also provided are pharmaceutical compositions comprising a recombinant adeno-associated virus of the invention and a pharmaceutically acceptable carrier or excipient. These pharmaceutical compositions may be useful in gene therapy for the treatment of PA caused by mutations in propionyl-CoA carboxylase -subunit (PCCA) or mutations in propionyl-CoA carboxylase -subunit (PCCB).