Comparative multi-goal tradeoffs in systems engineering of microbial metabolism

Abstract

BackgroundMetabolic engineering design methodology has evolved from using pathway-centric, random and empirical-based methods to using systems-wide, rational and integrated computational and experimental approaches. Persistent during these advances has been the desire to develop design strategies that address multiple simultaneous engineering goals, such as maximizing productivity, while minimizing raw material costs.ResultsHere, we use constraint-based modeling to systematically design multiple combinations of medium compositions and gene-deletion strains for three microorganisms (Escherichia coli, Saccharomyces cerevisiae, and Shewanella oneidensis) and six industrially important byproducts (acetate, D-lactate, hydrogen, ethanol, formate, and succinate). We evaluated over 435 million simulated conditions and 36 engineering metabolic traits, including product rates, costs, yields and purity.ConclusionsThe resulting metabolic phenotypes can be classified into dominant clusters (meta-phenotypes) for each organism. These meta-phenotypes illustrate global phenotypic variation and sensitivities, trade-offs associated with multiple engineering goals, and fundamental differences in organism-specific capabilities. Given the increasing number of sequenced genomes and corresponding stoichiometric models, we envisage that the proposed strategy could be extended to address a growing range of biological questions and engineering applications.

Enhanced production of heterologous proteins by a synthetic microbial community: Conditions and trade-offs

“…However, the acetate overflow that sustains the cleaner growth at such high rates subtracts significant amounts of glucose from conversion into the target protein, which results in yield loss. The rate-yield trade-off is well-known in metabolic engineering [39] and has been extensively studied in microbial physiology [40], mostly in the context of single species or strains. We here show that this trade-off also appears on the community level, when weighing the costs of sustaining a cleaner population against the benefits of increased protein production.…”

Synthetic Ecology of Microbes: Mathematical Models and Applications

“…However, the efficient microbial conversion of complex biological feedstock to desired products typically requires multiple different functionalities. This poses a challenge in engineering monocultures as optimizing a single species for one trait usually comes at the expense of other traits due to the existence of tradeoffs in the performance limits of different functional traits 6; 81; 82 . These difficulties have attracted researchers to the challenge of designing synthetic consortia-based microbial cell factories with task-specialized species.…”

Genome scale models of yeast: towards standardized evaluation and consistent omic integration

“…Intracellular fluxes can be quantified using 13 18,95,146,147,155,156 . Intracellular fluxes can be quantified using 13 18,95,146,147,155,156 .…”