Abstract: MATH/CHEM/COMP 2002, Dubrovnik, June 24-29, 2002

Expanding the Genetic Code

Nediljko BudiSa

Max-Planck-Institut fuer Biochemie, Abteilung Strukturforschung, Am Klopferspitz 18a, 82152 Martinsried, Germany

Our current experimental efforts for the genetic code changes in living cells are intended to expand greatly the number of amino acids as basic substrates in the ribosome-mediated protein synthesis by novel codon reassignments beyond 20 canonical amino acids prescribed by the genetic code.  We have developed selective pressure incorporation (SPI) method with which a full preference for the incorporation of non-canonical amino acids over canonical ones can be obtained. To expand further potentials of this methodology we are trying by use of various engineering approaches to create host cells with altered protein translation components i.e. reprogrammed hybrid translational system which would efficiently generate proteins with completely new chemistry unseen in nature. These include attempts to engineer aminoacyl-tRNA synthetases with relaxed and new substrate specificities as well as introduction of orthogonal aminoacyl-tRNA synthetase - tRNA pairs in the protein translation  process in vivo.