The present disclosure relates to a microorganism producing O-acetylhomoserine with high efficiency and a method for producing O-acetylhomoserine and L-methionine using the microorganism. The present disclosure provides a microorganism producing O-acetylhomoserine having an enhanced activity of a protein which is predicted to export O-acetylhomoserine, and a method for producing O-acetylhomoserine and L-methionine using the microorganism.

In certain aspects the methods comprise administering an inhibitor of hydrogen sulfide biosynthesis, a cystathionine--synthase (CBS) inhibitor, or a hydrogen sulfide neutralizing agent to a patient having a cancer associated with elevated production of hydrogen sulfide.

The present disclosure relates to erythroid cells that have been engineered to express a homocysteine reducing polypeptide, or a variant thereof, or a homocysteine degrading polypeptide, or a variant thereof. The engineered erythroid cells may further comprise an amino acid transporter, for example a homocysteine transporter or a serine transporter, or a cystathionine degrading polypeptide. The engineered erythroid cells of the present disclosure are useful in reducing the level of homocysteine in a subject. The engineered erythroid cells of the present disclosure are further useful in methods of treating homocystinuria.

In certain aspects the methods comprise administering an inhibitor of hydrogen sulfide biosynthesis, a cystathionine--synthase (CBS) inhibitor, or a hydrogen sulfide neutralizing agent to a patient having a cancer associated with elevated production of hydrogen sulfide.

Human cystathionine -synthase variants are disclosed, as well as a method to produce recombinant human cystathionine -synthase and variants thereof. More particularly, the role of both the N-terminal and C-terminal regions of human CBS has been studied, and a variety of truncation mutants and modified CBS homologs are described. In addition, a method to express and purify recombinant human cystathionine -synthase (CBS) and variants thereof which have only one or two additional amino acid residues at the N-terminus are described.

Provided herein are improved compositions and methods for enzyme replacement therapy using modified human cystathionine beta synthase (CBS) in the treatment of homocystinuria and related diseases and disorders.

Provided herein are improved compositions and methods for enzyme replacement therapy using modified human cystathionine beta synthase (CBS) in the treatment of homocystinuria and related diseases and disorders.

The present invention provides a method of PEGylating a human truncated cystathionine ?-synthase protein containing a mutation of a cysteine to a serine at amino acid position 15 (htCBS C15S). The htCBS C15S was PEGylated with one of 5 kDa, 10 kDa, or 20 kDa NHS ester PEG molecules. In-process monitoring of the PEGylation process was used in the method to reduce levels of unPEGylated htCBS C15S and htCBS C15S with insufficient PEGylation. Administration of the PEGylated htCBS C15S had efficacy throughout the course of treatment for homocystinuria.

This invention provides chromatographic methods for the purification of a cystathionine -Synthase (CBS) protein, particularly truncated variants thereof and compositions and pharmaceutical compositions prepared therefrom.

This invention provides chromatographic methods for the purification of a cystathionine -Synthase (CBS) protein, particularly truncated variants thereof and compositions and pharmaceutical compositions prepared therefrom.