Compositions, methods, and systems for modifying sterol metabolism in a subject is disclosed. In some embodiments, the subjects may be administered one or more mammalian cells modified to express at least one sterol degrading enzyme derived from a bacterium. In many embodiments, the cell is a macrophage or monocyte stably expressing three or more enzymes that aid in opening the β ring of cholesterol. The disclosed compositions and methods may be useful in lowering cholesterol levels in a subject in need thereof. In some embodiments, the subject may have a genetic predisposition to atherosclerosis.

Compositions, methods, and systems for modifying sterol metabolism in a subject is disclosed. In some embodiments, the subjects may be administered one or more mammalian cells modified to express at least one sterol degrading enzyme derived from a bacterium. In many embodiments, the cell is a macrophage or monocyte stably expressing three or more enzymes that aid in opening the β ring of cholesterol. The disclosed compositions and methods may be useful in lowering cholesterol levels in a subject in need thereof. In some embodiments, the subject may have a genetic predisposition to atherosclerosis.

The present invention concerns a genetically modified bacterium and to its industrial application, in particular in the 1,2-dehydrogenation of steroids.

A genetically-modified bacterium, for example of the class Actinobacteria, and the use of such a bacterium in the bioconversion of a steroidal substrate into a steroidal product of interest. A method of converting a steroidal substrate into a steroidal product of interest, wherein the method comprises: inoculating culture medium with genetically-modified bacteria according to any of Claims 1 to 28 and growing the bacterial culture until a target OD.sub.600 is reached; adding a steroidal substrate to the bacterial culture when the target OD.sub.600 is reached; culturing the bacterial culture so that the steroidal substrate is converted to the steroidal product of interest; and extracting and/or purifying the steroidal product of interest from the bacterial culture.

Disclosed herein are compositions, constructs, cassettes, vectors, cells, nucleic acids, peptides, proteins, protocols and methods for reducing cholesterol and lipid buildup in mammalian subjects, via gene and/or cell therapeutic treatments. In many embodiments, the disclosed compositions, cells, constructs, cassettes, vectors, nucleic acids, peptides, proteins, protocols and methods may help to reduce lipid levels in mammals. In one embodiment, the disclosed compositions, cells, constructs, cassettes, vectors, nucleic acids, peptides, proteins, protocols and methods are useful in reducing lipid build-up, especially cholesterol, in liver cells.

Compositions, methods, and systems for modifying sterol metabolism in a subject is disclosed. In some embodiments, the subjects may be administered one or more mammalian cells modified to express at least one sterol degrading enzyme derived from a bacterium. In many embodiments, the cell is a macrophage or monocyte stably expressing three or more enzymes that aid in opening the ring of cholesterol. The disclosed compositions and methods may be useful in lowering cholesterol levels in a subject in need thereof. In some embodiments, the subject may have a genetic predisposition to atherosclerosis.

Provided are biosynthetic processes for producing sterol derivatives, and to non-naturally occurring organisms capable of producing sterol derivatives. More specifically, genetically modified non-naturally occurring organisms for producing KCEA, KCDA, and related compounds, from cholesterol, ?-sitosterol, campesterol and their analogs, are provided.

The disclosed compositions, methods, and systems are useful in treating and preventing various cancers associated with buildup of mitochondrial cholesterol. In many embodiments, the disclosed compositions, methods, and systems may improve the efficacy and cytotoxicity of chemotherapeutic compounds, for example increasing cellular sensitivity to chemotherapy and/or reducing or preventing resistance. In many embodiments, the cancer may be early or late stage hepatocellular carcinoma.

Disclosed herein are compositions, methods, and systems for enhancing cholesterol degradation in a cell, tissue, or organism. In many embodiments, the disclosure describes the use of one or more proteins, or sequences coding therefor, to enhance flow of cholesterol into the mitochondrion, where the cholesterol is degraded by one or more proteins comprising bacteria-related sequences. The compositions, methods, and systems disclosed herein are useful in the prevention or treatment of diseases, disorders, and conditions associated with high levels of cholesterol in the blood or cells of a patient.

Compositions, methods, and systems for modifying sterol metabolism in a subject is disclosed. In some embodiments, the subjects may be administered one or more mammalian cells modified to express at least one sterol degrading enzyme derived from a bacterium. In many embodiments, the cell is a macrophage or monocyte stably expressing three or more enzymes that aid in opening the ring of cholesterol. The disclosed compositions and methods may be useful in lowering cholesterol levels in a subject in need thereof. In some embodiments, the subject may have a genetic predisposition to atherosclerosis.