Optknock: A bilevel programming framework for identifying gene knockout strategies for microbial strain optimization

2003/10/07 by Anthony P. Burgard, Priti Pharkya, Costas D. Maranas · 1,290 citations
Biochemistry, Genetics and Molecular Biology · Chemistry · Engineering · #Adaptation (eye) #Biochemical engineering #Biochemistry #Biofuel production and bioconversion #Biology #Chemistry #Computational biology #Enzyme Catalysis and Immobilization #Gene #Gene knockout #Metabolic engineering #Microbial Metabolic Engineering and Bioproduction #Mutant #Overproduction #Strain (injury)

paper · doi:10.1002/bit.10803

published in Biotechnology and Bioengineering 84(6), 647-657 (Wiley)

openalex publication_date 2003/10/07 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28

Abstract

The advent of genome-scale models of metabolism has laid the foundation for the development of computational procedures for suggesting genetic manipulations that lead to overproduction. In this work, the computational OptKnock framework is introduced for suggesting gene deletion strategies leading to the overproduction of chemicals or biochemicals in E. coli. This is accomplished by ensuring that a drain towards growth resources (i.e., carbon, redox potential, and energy) must be accompanied, due to stoichiometry, by the production of a desired product. Computational results for gene deletions for succinate, lactate, and 1,3-propanediol (PDO) production are in good agreement with mutant strains published in the literature. While some of the suggested deletion strategies are straightforward and involve eliminating competing reaction pathways, many others suggest complex and nonintuitive mechanisms of compensating for the removed functionalities. Finally, the OptKnock procedure, by coupling biomass formation with chemical production, hints at a growth selection/adaptation system for indirectly evolving overproducing mutants.

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