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Expanded Genetic Code in a Bacterium Creating a Miniature Factory Expanding the Genetic Code • At the Scripps Institute in California, scientists have engineered a bacterium with an expanded genetic code. • In addition to A, T, G, and C, they have added to synthetic nucleotides: d5SICS and dNaM (known as Y and X for short). E coli with Expanded Genome The synthetic nucleotides have been created in such a way that they are not rejected by DNA Polymerase when it is proofreading during DNA Replication. The cells naturally took the new nitrogen bases into their genome They made matching base pairs that face each other on either side of the DNA double helix. Factory Microbes • The goal is for the cells with the synthetic nucleotides to begin to produce “unnatural proteins.” • Naturally, only 20 amino acids are produced, cells with the two new nucleotides can produce up to 152 types of amino acids. The Factories and Natural Selection • Because they are alive, the microbial factories could harness the power of evolution to rapidly select and automatically find the most useful (fittest) metabolic pathways to making the desired proteins. – Cells could produce thousands of variations on a successful antibiotic in a fraction of the time it would take traditional chemists. – The 1000s of variations would then be subjected to selection pressure to find the most effective and efficiently made variants.