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首页> 外文期刊>Journal of Mathematical Biology >Optimal control of bacterial growth for the maximization of metabolite production
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Optimal control of bacterial growth for the maximization of metabolite production

机译：细菌生长的最大控制最大化代谢产量

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摘要

Microorganisms have evolved complex strategies for controlling the distribution of available resources over cellular functions. Biotechnology aims at interfering with these strategies, so as to optimize the production of metabolites and other compounds of interest, by (re)engineering the underlying regulatory networks of the cell. The resulting reallocation of resources can be described by simple so-called self-replicator models and the maximization of the synthesis of a product of interest formulated as a dynamic optimal control problem. Motivated by recent experimental work, we are specifically interested in the maximization of metabolite production in cases where growth can be switched off through an external control signal. We study various optimal control problems for the corresponding self-replicator models by means of a combination of analytical and computational techniques. We show that the optimal solutions for biomass maximization and product maximization are very similar in the case of unlimited nutrient supply, but diverge when nutrients are limited. Moreover, external growth control overrides natural feedback growth control and leads to an optimal scheme consisting of a first phase of growth maximization followed by a second phase of product maximization. This two-phase scheme agrees with strategies that have been proposed in metabolic engineering. More generally, our work shows the potential of optimal control theory for better understanding and improving biotechnological production processes.
机译：微生物具有在蜂窝功能上控制可用资源分布的复杂策略。生物技术旨在干扰这些策略，以优化代谢物和其他感兴趣的化合物，通过（RE）工程来工程细胞的潜在调节网络。由此称为简单的自助复制器模型可以描述所得到的资源重新分配，以及作为动态最佳控制问题的利益产品的合成的最大化。最近的实验工作的动机，我们专门对代谢物生产的最大化感兴趣，因为可以通过外部控制信号关闭生长。我们通过分析和计算技术的组合研究了相应的自助复制器模型的各种最佳控制问题。我们表明，在无限营养供应的情况下，用于生物质最大化和产品最大化的最佳解决方案非常相似，但营养物质有限时偏离。此外，外部生长控制覆盖自然反馈生长控制，并导致最佳方案，其由生长最大化的第一阶段，然后是产品最大化的第二阶段。这种两阶段方案同意代谢工程中提出的策略。更一般地，我们的工作表明了最佳控制理论的潜力，以便更好地理解和改善生物技术生产过程。

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