Floyd ROMESBERG - A Semi-synthetic Organism with an Expanded Genetic Alphabet
Channel: Institut des Hautes Études Scientifiques (IHÉS)
Date: 2015-12-21

Expansion  of  the  genetic  alphabet  to  include  a  third  base pair not  only  has immediate    utility    for    a    number    of applications,    such    as    site-specific oligonucleotide  labeling, but  also  serves  as  the  foundation  for  an  organism  with an expanded genetic code. Toward this goal, we have examined a large number of different  unnatural  nucleotides  bearing  mainly  hydrophobic  nucleobase  analogs that  pair  based  on  packing  and  hydrophobic  interactions  rather  than  H-bonding. 
Optimization  based  on  extensive  structure-activity  relationship  studies  and  two screens resulted in the identification of a class of unnatural base pairs that are well recognized  by  DNA  and  RNA  polymerases.  More  recently,  we  have  engineered E.  coli to  import  the  requisite  unnatural  triphosphates  and  shown  that  DNA containing the unnatural base pair is efficiently rep
licated within the cell, resulting in  the  first  semi-synthetic  organism  that  stores  increased  information  in  its genome.