Predictive dynamic control accurately maps the design space for 2,3-butanediol production

Area of Science:

• Biotechnology and metabolic engineering
• Chemical engineering and process optimization
• Synthetic biology

Background:

• 2,3-Butanediol (2,3-BDO) is a versatile platform chemical with significant industrial applications.
• Traditional petroleum-based production is environmentally unsustainable.
• Fermentation offers an ecologically superior alternative, but requires process optimization for economic feasibility.

Purpose of the Study:

• To adapt and apply dynamic control flux-balance analysis (dcFBA) for optimizing 2,3-butanediol production in E. coli.
• To identify optimal conditions for maximizing 2,3-BDO titer and productivity.
• To enhance the economic viability of biotechnological production processes.

Main Methods:

• Simulations of two-stage fed-batch processes using dcFBA to explore the solution space.
• Identification of proportionality and trade-off regions for process optimization.
• Experimental validation of simulated optimal conditions.
• Optimization of a continuous two-reactor process for enhanced productivity.

Main Results:

• dcFBA simulations identified distinct regions influencing 2,3-BDO production strategies.
• Experimental validation achieved high titer (Image 1) and productivity (Image 2).
• Continuous two-reactor optimization increased productivity over threefold with minimal impact on titer and yield.

Conclusions:

• Dynamic control flux-balance analysis (dcFBA) is an effective tool for optimizing biotechnological production processes.
• The developed optimization strategy significantly improves 2,3-butanediol production efficiency.
• This approach can contribute to making numerous biotechnological productions economically feasible.