Thursday, August 14, 2008 - 4:00 PM

Harnessing Constructive Biology in Metabolic Engineering Applications

Brian M. Baynes, Codon Devices, Inc., 1 Kendall Square, Bldg 300, Cambridge, MA 02139

Modern constructive biology techniques accelerate metabolic engineering R&D by facilitating the design, construction, and engineering of functional biological systems. Historically, it was not possible to test a complex set of metabolic hypotheses with uncertainty, because the available genome engineering tools only allowed a small number of directed hypotheses or a large number of random hypotheses to be tested. Now, new methods for high throughput DNA construction make it possible to construct high quality genetic material in the kilobase to megabase length range at low cost. This enables hypotheses from computational designs and bioinformatics analyses to be instantiated quickly and experimentally tested in a directed and scalable way. The resulting data sets contain greater information content and can be used to refine design rules, accelerating future designs. We have used these approaches in genome engineering contexts such as promoter and enzyme engineering for properties including expression yield, catalytic activity, and specificity; and operon engineering for properties such as yield and flux.