Metabolic engineering to increase crop yield: From concept to execution

[Display omitted] •Rational design strategies are needed to engineer complex traits such as yield.•Predictive models facilitate the identification of gene targets.•Flux balance models provide a metabolic perspective.•Regulatory association networks provide a transcriptome based viewpoint.•The method for trait engineering can affect the commercialization cost and timeline. Although the return on investment over the last 20 years for mass screening of individual plant genes to improve crop performance has been low, the investment in these activities was essential to establish the infrastructure and tools of modern plant genomics. Complex traits such as crop yield are likely multigenic, and the exhaustive screening of random gene combinations to achieve yield gains is not realistic. Clearly, smart approaches must be developed. In silico analyses of plant metabolism and gene networks can move a trait discovery program beyond trial-and-error approaches and towards rational design strategies. Metabolic models employing flux-balance analysis are useful to determine the contribution of individual genes to a trait, or to compare, optimize, or even design metabolic pathways. Regulatory association networks provide a transcriptome-based view of the plant and can lead to the identification of transcription factors that control expression of multiple genes affecting a trait. In this review, the use of these models from the perspective of an Ag innovation company’s trait discovery and development program will be discussed. Important decisions that can have significant impacts on the cost and timeline to develop a commercial trait will also be presented.