AUTHOR=Heinsch Stephen C. , Das Siba R. , Smanski Michael J. TITLE=Simulation Modeling to Compare High-Throughput, Low-Iteration Optimization Strategies for Metabolic Engineering JOURNAL=Frontiers in Microbiology VOLUME=9 YEAR=2018 URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2018.00313 DOI=10.3389/fmicb.2018.00313 ISSN=1664-302X ABSTRACT=

Increasing the final titer of a multi-gene metabolic pathway can be viewed as a multivariate optimization problem. While numerous multivariate optimization algorithms exist, few are specifically designed to accommodate the constraints posed by genetic engineering workflows. We present a strategy for optimizing expression levels across an arbitrary number of genes that requires few design-build-test iterations. We compare the performance of several optimization algorithms on a series of simulated expression landscapes. We show that optimal experimental design parameters depend on the degree of landscape ruggedness. This work provides a theoretical framework for designing and executing numerical optimization on multi-gene systems.