In vivo catalysis of a metabolically essential reaction by an antibody

Tang, Y., Hicks, J. B., Hilvert, D. (1991) In vivo catalysis of a metabolically essential reaction by an antibody. Proceedings of the National Academy of Sciences of the United States of America, 88 (19). pp. 8784-8786. ISSN 00278424 (ISSN)

URL: http://www.ncbi.nlm.nih.gov/pubmed/1924339

Abstract

We have established a growth selection requirement for a catalytic antibody with modest chorismate mutase activity. Conversion of (-)-chorismate into prephenate is the key step in the biosynthesis of the aromatic amino acids tyrosine and phenylalanine. Strains of the yeast Saccharomyces cerevisiae containing an insertion mutation in the structural gene for the enzyme chorismate mutase (EC 5.4.99.5) require exogenous supplements of these two amino acids for efficient growth. Intracellular expression of the heterologous antibody catalyst in one such strain, identified by random mutagenesis and genetic selection, provides a substantial growth advantage under auxotrophic conditions; complementation was not observed with an unrelated esterolytic antibody. In addition to demonstrating that tailored immunoglobulin catalysts can carry out vital biochemical reactions in vivo, these experiments provide a powerful selection assay for identifying genetic changes within the antibody molecule itself that augment chemical efficiency.

Item Type: Paper
Uncontrolled Keywords: antibody chorismate mutase article catalysis nonhuman priority journal saccharomyces cerevisiae Antibodies Chorismic Acid Cloning, Molecular Genetic Complementation Test Immunoglobulins, Fab Recombinant Proteins Support, Non-U.S. Gov't Support, U.S. Gov't, Non-P.H.S.
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > monoclonal antibody
CSHL Authors:
Communities: CSHL labs > Hicks lab
Depositing User: Matt Covey
Date: 1991
Date Deposited: 09 Aug 2013 20:53
Last Modified: 12 Aug 2013 15:24
Related URLs:
URI: http://repository.cshl.edu/id/eprint/28533

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