Princeton University    Office of Technology Licensing and Intellectual Property

                                                                Fourth Floor, New South Building

                                                                Post Office Box 36

                                                                Princeton, New Jersey 08544-0036

                                                                Phone: (609) 258-6762

                                                                FAX: (609) 258-1159

 

 

COMPOSITIONS AND METHODS FOR MODULATING LYSINE PRODUCTION

Princeton University Invention # 05-2191

 

           

L,L-diaminopimelic acid aminotransferase, a key enzyme in a new variant of the lysine biosynthesis pathway was discovered by researchers at Princeton University and Rutgers University. The gene for this enzyme was also identified and cloned from the experimental plant Arabidopsis thaliana by researchers at Rutgers.  Homologs of the gene have been identified in the genomes of major crop plants, algae, cyanobacteria, archaea, and in pathogenic microorganisms. This discovery demonstrates that plants and specific microbial pathogens use a novel pathway for lysine biosynthesis, which is different from previously known pathways in bacteria and fungi. The discovery opens the possibility of specifically manipulating the growth and properties of species carrying the unique lysine biosynthesis pathway reported here.

 

Lysine is important to humans on a number of counts.  It is required for protein synthesis. The lysine biosynthesis pathway has been a prime target for discovery of antibiotics against pathogenic microorganisms since a part of the pathway is used for the synthesis of the peptidoglycan cell wall component. Lysine is also an essential nutrient for animals.  The content of lysine limits the nutritional value of crop plants.  Because of its importance in plant growth lysine biosynthesis is a prime target for development of antibiotics, agricultural herbicides, and algaecides.

 

All of the above mentioned areas are potential targets for commercial development.  Improvement of the nutritional value of crops is currently a major goal for agricultural companies.  Fermentative production of lysine for sale as a nutritional supplement is a major industry.  Antibiotics are also of major importance in both medicine, where they are used to counteract bacterial infections, and in agriculture or environmental applications, where they are used to eliminate weeds (herbicides) or algae (algaecides). Antibiotics, herbicides and algaecides together comprise major industries world-wide.  Commercial exploitation of lysine biosynthesis depends on detailed knowledge of the biosynthesis pathway.  Until the discovery that is presented in this invention it was unclear exactly how lysine is synthesized by plants.  Moreover, although the lysine biosynthesis pathway of certain bacteria was known, it was not obvious that other prokaryotic species have a different lysine biosynthesis pathway with greater similarity to the plant pathway.  This discovery has solved the question about the genetic basis for lysine biosynthesis in plants.  Moreover, the discovery points to the possibility that a plant-like lysine biosynthesis pathway exists in some prokaryotic organisms including pathogens. Indeed a number of chlamydia organisms have been shown to utilize this newly discovered pathway. It should also be noted that the crystal structure of the A. thaliana enzyme has been determined.

 

Princeton is currently seeking industrial collaboration to commercialize this technology. Patent protection is pending.

 

 

Publications and References:

 

McCoy AJ, Adams NE, Hudson AO, Gilvarg C, Leustek T, Maurelli AT, L,L-diaminopimelate aminotransferase, a trans-kingdom enzyme shared by Chlamydia and plants for synthesis of diaminopimelate/lysine, Proc Natl Acad Sci U S A. 2006 Nov 21;103(47):17909-14. Epub 2006 Nov 8

 

 

Hudson AO, Singh BK, Leustek T, Gilvarg C, An LL-diaminopimelate aminotransferase defines a novel variant of the lysine biosynthesis pathway in plants. Plant Physiol. 2006 Jan;140(1):292-301. Epub 2005 Dec 16

 

Hudson AO, Bless C, Macedo P, Chatterjee SP, Singh BK, Gilvarg C, Leustek T.

Biosynthesis of lysine in plants: evidence for a variant of the known bacterial pathways. Biochim Biophys Acta. 2005 Jan 18;1721(1-3):27-36. Epub 2004 Nov 4.

 

Watanabe N, Cherney M, Van Belkum M, Marcus S, Flegel M, Clay M, Deyholos M, Vederas J, James M, Crystal Structure of ll-Diaminopimelate Aminotransferase from Arabidopsis Thaliana: A Recently Discovered Enzyme in the Biosynthesis of l-Lysine by Plants and Chlamydia. J. Mol Bio. 2007 available on line   

 

 

For more information on Princeton University invention # 05-2191 please contact:

 

                        Laurie Tzodikov

                        Office of Technology Licensing and Intellectual Property

                        Princeton University

                        4 New South Building

                        Princeton, NJ 08544-0036

                        (609) 258-7256

                        (609) 258-1159 fax

                        tzodikov@princeton.edu