Considerable effort is currently directed to engineer micro-organisms to produce useful chemicals. The greatest potential environmental benefit of metabolic engineering would be the production of high volume commodity chemicals, such as biofuels. Yet the high yields required for the economic viability of low-value chemicals are particularly hard to achieve in microbes due to the myriad competing biochemical pathways. We are developing an alternative approach, which we call synthetic biochemistry. Synthetic biochemistry throws away the cells and builds biochemical pathways in reaction vessels using complex mixtures of isolated enzymes. As the only pathway in the vessel is the desired transformation, yields can approach 100%. The challenge for synthetic biochemistry is to replace the complex regulatory systems that exist in cells in a simplified form. We are designing and testing various ideas for building highly robust systems that can operate continuously for long periods of time.