S14: Rational design of microorganisms for efficient secondary metabolite synthesis

Elementary Mode Analysis (EMS) is a useful tool for predicting efficient pathways and for guiding metabolic engineering manipulations to improve strains.  Several successful cases related to primary metabolism have been demonstrated.  In this presentation we demonstrate that EMA is also an efficient tool for the rational strain development to enhance secondary metabolite production. As a case study, EMA was applied to the metabolic network of recombinant E. coli expressing a pathway for diapolycopendioic acid (DPA). A set of eight gene deletions resulting in efficient DPA synthesis pathways was identified. A strain containing a combination of these eight gene deletions can function according to five pathways that support cell function for growth and for efficient production of DPA. Such mutant produces DPA at significantly increased yields and rates in comparison to the wild-type. The consistency between model prediction and experimental results confirms the validity of the EMA strategy for the rational design of efficient organisms.