Progress in genome sequencing, systems approaches and high throughput genomic and proteomic technologies is outpacing our ability to test many hypotheses.  These hypotheses are now limited by bottlenecks in the construction of new genetic elements, pathways and cells.  To address this challenge, we are developing new methods that combine large-scale DNA synthesis techniques with engineered recombination strategies to manipulate native genomes and introduce synthetic DNA elements to alter the endogenous genetic code of organisms.  Specifically, we are engineering strains of Escherichia coli in which the entire genome is recoded, leaving some codons unused by the native translational machinery.  These codons can be reallocated for a broad set of applications, such as the incorporation of nonnatural amino acids with novel biochemical properties.  To achieve this goal, we integrate computer-aided design software, microarray-oligonucleotides, multiplex DNA synthesis, DNA error correction and homologous recombination to provide a resource for full genome re-synthesis and remodeling. I will present our progress toward a recoded E. coli (rE.coli) with complete replacement of the least frequent stop codon (amber, i.e. UAG; ~300 instances) with the most common stop codon (ochre, i.e. UAA).