Constructive Biosynthesis Subgroup

Over 60 years ago, a theory was proposed as to the origin of biosynthetic pathways: Complexity begets simplicity, biosynthetic pathways evolve in reverse from complex molecules to simpler and simpler ones.

This hypothesis, is referred to as the retro-evolution hypothesis, and represents the first theory for how biosynthetic pathways evolve de novo. In 2010, we advanced the concept, which we call bioretrosynthesis, in commentary in Nature Chemical Biology of adapting this hypothesis for the engineering of new biosynthetic pathways, and in 2013, the Bachmann group published the first application of this hypothesis to artificially evolve a biosynthetic pathway for the generation of an unnatural product, in this case an AIDS drug called didanosine.

Didanosine is currently manufactured chemically and is extremely expensive to product. Indeed the raw material and manufacturing costs alone on a per dose basis, exceed the capability of patients in need to afford this drugs. Our work provides the first step in converting this expensive process into a green economical biological process to generate these life-saving compound by fermentation.