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