In 2014 the technique was used to produce the HIV drug didanosine: a simpler molecule was identified that can be converted into didanosine when subjected to a specific chemical transformation in the presence of a specific enzyme. The gene that creates the enzyme was then "copied", adding random mutations to each copy using ribokinase engineering. The mutant genes were inserted into Escherichia coli bacteria and used to produce (now-mutant) enzymes. The enzymes were then mixed with the precursor and the mutant enzymes that produced the greatest amount of didanosine were retained and replicated. One mutant stimulated a 50x increase in didanosine production. The first step was repeated, using the first precursor in place of didanosine, finding a yet simpler precursor and an enzyme to produce it. One mutated enzyme produced a 9,500x increase in nucleoside production. A third retrogression allowed them to start with the simple and inexpensive sugar named dideoxyribose and produce didanosine in a three-step sequence.