Bioretrosynthesis is a technique for synthesizing organic chemicals from inexpensive precursors and evolved enzymes. The technique builds on the retro-evolution hypothesis proposed in 1945 by geneticist Norman Horowitz.
The technique works backwards from the target to identify a precursor molecule and an enzyme that converts it into the target, and then a second precursor that can produce the first and so on until a simple, inexpensive molecule becomes the beginning of the series.
For each precursor, the enzyme is evolved using induced mutations and natural selection to produce a more productive version. The evolutionary process can be repeated over multiple generations until acceptable productivity is achieved.
The process does not require high temperature, high pressure, the use of exotic catalysts or other elements that can increase costs.
The enzyme "optimizations" that increase the production of one precursor from another are cumulative in that the same precursor productivity improvements can potentially be leveraged across multiple target molecules.
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.
- "The bioretrosynthesis solution: shifting evolution into reverse to make cheaper drugs". KurzweilAI. 2014-04-09. doi:10.1038/nchembio.1494. Retrieved 2014-04-09.
Birmingham, W. R.; Starbird, C. A.; Panosian, T. D.; Nannemann, D. P.; Iverson, T. M.; Bachmann, B. O. (2014). "Bioretrosynthetic construction of a didanosine biosynthetic pathway". Nature Chemical Biology. 10: 392–399. doi:10.1038/nchembio.1494. PMC 4017637. PMID 24657930.
- "Shifting evolution into reverse promises cheaper, greener way to make new drugs". ScienceDaily. doi:10.1038/nchembio.1494. Retrieved 2014-04-09.
- "Bio-RetroSynthesis Team — Institute of Systems & Synthetic Biology". Issb.genopole.fr. Retrieved 2014-04-09.