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Keywords:

  • Biochemical engineering;
  • Evolutionary game theory;
  • Extracellular enzymes;
  • Optimization of enzyme synthesis;
  • Systems biology

Abstract

The engineering of microorganisms to produce a variety of extracellular enzymes (exoenzymes), for example for producing renewable fuels and in biodegradation of xenobiotics, has recently attracted increasing interest. Productivity is often reduced by “cheater” mutants, which are deficient in exoenzyme production and benefit from the product provided by the “cooperating” cells. We present a game-theoretical model to analyze population structure and exoenzyme productivity in terms of biotechnologically relevant parameters. For any given population density, three distinct regimes are predicted: when the metabolic effort for exoenzyme production and secretion is low, all cells cooperate; at intermediate metabolic costs, cooperators and cheaters coexist; while at high costs, all cells use the cheating strategy. These regimes correspond to the harmony game, snowdrift game, and Prisoner's Dilemma, respectively. Thus, our results indicate that microbial strains engineered for exoenzyme production will not, under appropriate conditions, be outcompeted by cheater mutants. We also analyze the dependence of the population structure on cell density. At low costs, the fraction of cooperating cells increases with decreasing cell density and reaches unity at a critical threshold. Our model provides an estimate of the cell density maximizing exoenzyme production.