Can a heterotrophic organism be evolved to synthesize biomass directly from CO2? In this talk, I demonstrate how a combination of rational metabolic rewiring, recombinant expression and laboratory evolution has led to the biosynthesis of sugars and other major biomass constituents, by a fully functional Calvin-Benson-Bassham cycle in E. coli. I will describe the genetic basis for the adaptation of E. coli to sugar synthesis from CO2.