Dynamic strain scanning optimization: an efficient strain design strategy for balanced yield, titer, and...

In recent years, constraint-based metabolic models have emerged as an important tool for metabolic engineering; a number of computational algorithms have been developed for identifying metabolic engineering strategies where the production of the desired chemical is coupled with the growth of the organism. A caveat of the existing algorithms is that they do not take the bioprocess into consideration; as a result, while the product yield can be optimized using these algorithms, the product titer and productivity cannot be optimized. In order to address this issue, we developed the Dynamic Strain Scanning Optimization (DySScO) strategy, which integrates the Dynamic Flux Balance Analysis (dFBA) method with existing strain algorithms.

In order to demonstrate the effective of the DySScO strategy, we applied this strategy to the design of Escherichia coli strains targeted for succinate and 1,4-butanediol production respectively. We evaluated consequences of the tradeoff between growth yield and product yield with respect to titer and productivity, and showed that the DySScO strategy is capable of producing strains that balance the product yield, titer, and productivity. In addition, we evaluated the economic viability of the designed strain, and showed that the economic performance of a strain can be strongly affected by the price difference between the product and the feedstock.

Our study demonstrated that the DySScO strategy is a useful computational tool for designing microbial strains with balanced yield, titer, and productivity, and has potential applications in evaluating the economic performance of the design strains.