Adaptive laboratory evolution (ALE) is a powerful tool to select for strains with growth-coupled phenotypes. When coupled with next-generation sequencing and omic technologies, genotype-to-phenotype relationships and the molecular mechanisms underlying desired complex phenotypes can now be uncovered using ALE. However, in order for ALE to be effective in generating strains with increased productivity, the product-of-interest needs to be coupled with cellular growth or survival. Advances in computational metabolic modeling can now identify metabolic engineering strategies to force the coupling of desired product formation with growth for a wide range of different compounds. Such strategies can potentially be coupled with ALE to further enhance productivity of microbial hosts. In addition to metabolic strategies, if the compound of interest is known to impart beneficial traits to the host, such as stress tolerance, then an environment can be designed to allow product formation to be coupled with growth or survival. This mini-review will cover recent advances in both the metabolic and environmental engineering and synthetic biology strategies to couple production with microbial fitness, successful cases for the use of these strategies with ALE to improve product formation, discuss limitations, and future perspectives.

中文翻译：

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生长耦合微生物生产的适应性实验室进化

适应性实验室进化 (ALE) 是选择具有生长耦合表型的菌株的强大工具。当与下一代测序和组学技术相结合时，现在可以使用 ALE 揭示基因型与表型的关系以及所需复杂表型背后的分子机制。然而，为了使 ALE 能够有效地产生具有更高生产力的菌株，感兴趣的产品需要与细胞生长或存活相结合。计算代谢建模的进步现在可以确定代谢工程策略，以强制将所需产物的形成与各种不同化合物的生长相结合。这种策略可能与 ALE 结合使用，以进一步提高微生物宿主的生产力。除了代谢策略，如果已知感兴趣的化合物可以赋予宿主有益的特性，例如抗逆性，那么可以设计一个环境，使产品形成与生长或存活相结合。这篇小型综述将涵盖代谢和环境工程以及合成生物学策略的最新进展，以将生产与微生物适应性相结合，将这些策略与 ALE 一起使用以改善产品形成的成功案例，讨论局限性和未来前景。