Methods and compositions relating to the engineering of an improved protein with homocyst(e)inase enzyme activity are described. For example, there are disclosed modified cystathionine-?-lyase (CGL) enzymes comprising one or more amino acid substitutions and capable of degrading homocyst(e)ine. Furthermore, provided are compositions and methods for the treatment of homocystinuria or hyperhomocysteinemia with homocyst(e)ine depletion using the disclosed enzymes or nucleic acids.

The present invention relates to nucleic acid constructs comprising selectable marker genes in a multicistronic transcription unit for use in the generation and selection of eukaryotic host cells for expression of a gene product of interest. For increased stringency of selection, the coding sequence of the selectable marker may be directed preceded by a relatively short functional open reading frame to reduce the efficiency of translation of the selectable marker, and/or the amino acid sequence of the selectable marker may comprise one or more mutations that reduce the level of resistance provide by the mutated marker as compared to its wild type counterpart. The invention further relates to methods for generating eukaryotic host cells for expression of a gene product of interest, wherein these nucleic acid constructs are used, and to methods for producing a gene product of interest wherein thus generated host cells are applied.

A method and composition for treating a cancerous tumor in a subject by targeting the tumor's vasculature using an enzyme conjugate comprising a ligand which binds to endothelial cells in the tumor vasculature and converts a prodrug administered to the subject into an anticancer drug in the tumor vasculature.

The present disclosure relates to methods for more efficiently recycling reduced electron carriers in a hydrogen-oxidizing microorganism with an operable Calvin-Benson cycle; synthetic carbon fixation pathways that recycle reduced electron carriers more efficiently than the Calvin-Benson cycle, such as methods for enzymatically converting carbon dioxide to formate and assimilating the resulting formate into central carbon metabolism; methods for producing biochemical products; and recombinant hosts utilizing one or more synthetic carbon fixation pathways.

Methods and compositions related to the engineering of a protein with L-cyst(e)ine degrading enzyme activity are described. For example, disclosed are modified cystathionine--lyases comprising one or more amino acid substitutions and capable of degrading L-cyst(e)ine. Furthermore, compositions and methods are provided for the treatment of cystinuria using the disclosed modified enzymes or nucleic acids encoding said enzymes.

Methods and compositions relating to the engineering of an improved protein with methionine--lyase enzyme activity are described. For example, in certain aspects there may be disclosed a modified cystathionine--lyase (CGL) comprising one or more amino acid substitutions and capable of degrading methionine. Furthermore, certain aspects of the invention provide compositions and methods for the treatment of cancer with methionine depletion using the disclosed proteins or nucleic acids.

Methods and compositions relating to the engineering of an improved protein with methionine--lyase enzyme activity are described. For example, in certain aspects there may be disclosed a modified cystathionine--lyase (CGL) comprising one or more amino acid substitutions and capable of degrading methionine. Furthermore, certain aspects of the invention provide compositions and methods for the treatment of cancer with methionine depletion using the disclosed proteins or nucleic acids.

Provided herein are cells, compositions, and related methods for improved cell growth. The expression of one or more of CBS, CTH, and GNMT genes is increased. In some embodiments, nucleic acid constructs, vectors, host cells and related compositions and methods for generating and selecting cysteine prototroph cells are provided.

A polypeptide fusion comprising a polypeptide having a C-terminus and a Thioesterification C-terminal Handle (TeCH-tag) fused to the C-terminus of the polypeptide, and a method of modifying the C-terminus of a polypeptide using the polypeptide fusion. The TeCH-tag comprises a sequence of formula (X),X, wherein X is any amino acid, n is an integer from 6 to 55, and X is an amino acid other than asparagine. The TeCH-tag is a substrate of an E1-like superfamily enzyme, and the method comprises reacting the polypeptide fusion, the E1-like superfamily enzyme, and ATP under conditions to O-AM Pylate the C-terminus of the polypeptide fusion; and reacting the C-terminally O-AM Pylated polypeptide fusion with a nucleophile comprising a functional group to provide a modified polypeptide fusion comprising the C-terminal functional group.

Genetically engineered immune cells, which express at least two metabolism modulating polypeptides and optionally a chimeric receptor polypeptide (e.g., an antibody-coupled T cell receptor (ACTR) polypeptide or a chimeric antigen receptor (CAR) polypeptide) capable of binding to a target antigen of interest. Also disclosed herein are uses of the engineered immune cells for inhibiting cells expressing a target antigen in a subject in need thereof.