Cell-free Scalability

Biotechnology has so far relied on microbes.  They produce beer, bread, cheese, yogurt, insulin, chemicals, flavors (like vanillin), and many other products.  Some of these microbes were found naturally and others were altered with metabolic engineering.  The output of a product from engineered microbes generally depends on the scale of the reaction.  On the lab scale, microbes may show high concentrations but when the bioreactor is scaled to industrial levels the concentrations drop.  This presents a major challenge for researchers engineering microbes.  Their lab scale microbes perform wonderfully but commercialization fails.  Cell-free synthetic biology is becoming an alternative to metabolic engineering.  Cell-free reactions only use parts of cells to carry out reactions, so nothing needs to be kept alive.  Additionally, the only reactions happening in the system are those that contribute to the desired product (when using cells many reactions are necessary to just keep the cells alive).  Cell-free reactions are easier to manipulate and quicker to run.  Fortunately they are also scale independent.

 Zawada et al. tested the scalability of cell-free reactions for cytokine production.  The plot to the right shows their main finding.  Concentrations of products are plotted versus time.  The different curves represent different scale reactions from 250 microliters to 100 liters.  Note that all the curves line up, so at any scale these reactions happen at the same rate (produce the same amount of product per time).  This is another benefit of using cell-free reactions.