Synthetic biology has been instrumental in turning microbes into cell-factories capable of diverse processes. A recent application has been to convert them into living therapeutics with diagnostic and production capabilities. These smart probiotics act as living medicines inside the body capable of diagnosing and responding to environmental cues in real time. Many companies and research groups have reported success with smart probiotics with several advancing to human clinical trials. Despite the promise, engineered probiotics are unable to replicate their functionality in a more complex environment. A rich environment, such as the gut, imposes restrictions on probiotic durability and effectiveness, hindering its ability to reach its full potential. Scientists have a plethora of advanced tools available today that enable enhanced strain engineering decisions to increase the production of fuels and commodity chemicals. However, these tools have not yet found mainstream application in building smart probiotics. Majority of the work in this field still relies on rational engineering. This review will propose strategies, with a focus on model-based approaches, that can help bridge the gap to systematic design and optimization of smart probiotics.

中文翻译：

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迈向智能益生菌的系统设计。

合成生物学在将微生物转变为能够进行多种过程的细胞工厂中发挥了作用。最近的应用是将它们转化为具有诊断和生产能力的活性疗法。这些智能益生菌可作为体内的活体药物，能够实时诊断和响应环境线索。许多公司和研究小组已经报告了智能益生菌的成功，其中一些正在推进人体临床试验。尽管有希望，但经过改造的益生菌无法在更复杂的环境中复制其功能。肠道等丰富的环境限制了益生菌的持久性和有效性，从而阻碍了其发挥其全部潜力的能力。如今，科学家拥有大量高级工具，这些工具可以使应变工程决策更加严格，从而增加燃料和日用化学品的产量。但是，这些工具尚未在构建智能益生菌中找到主流应用。该领域的大部分工作仍然依赖于合理的工程。这篇综述将提出策略，重点放在基于模型的方法上，可以帮助缩小智能益生菌的系统设计和优化之间的差距。