Biosensor-driven, model-based optimization of the orthogonally expressed naringenin biosynthesis pathway.

An efficient strategy, powered by orthogonal expression, was applied to successfully optimize a biosynthetic pathway for microbial production of flavonoids in E. coli up to high, competitive levels. Within this strategy, statistical learning techniques were combined with combinatorial pathway optimization techniques and an in vivo high-throughput screening method to efficiently determine the optimal operon configuration of the pathway. This "pathway architecture designer" workflow can be applied for the fast and efficient development of new microbial cell factories for different types of molecules of interest while also providing additional insights into the underlying pathway characteristics.