Simulation Modeling to Compare High-Throughput, Low-Iteration Optimization Strategies for Metabolic Engineering

Autor: Stephen C. Heinsch, Siba R. Das, Michael J. Smanski
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Frontiers in Microbiology, Vol 9 (2018)
Druh dokumentu: article
ISSN: 1664-302X
DOI: 10.3389/fmicb.2018.00313
Popis: 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.
Databáze: Directory of Open Access Journals