Abstract

There is an increasing demand for bioproducts produced by metabolically engineered microbes, such as pharmaceuticals, biofuels, biochemicals and other high value compounds. In order to meet this demand, modular optimization, the optimizing of subsections instead of the whole system, has been adopted to engineer cells to overproduce products. Research into modularity has focused on traditional approaches such as DNA, RNA, and protein-level modularity of intercellular machinery, by optimizing metabolic pathways for enhanced production. While research into these traditional approaches continues, limitations such as scale-up and time cost hold them back from wider use, while at the same time there is a shift to more novel methods, such as moving from episomal expression to chromosomal integration. Recently, nontraditional approaches such as co-culture systems and cell-free metabolic engineering (CFME) are being investigated for modular optimization. Co-culture modularity looks to optimally divide the metabolic burden between different hosts. CFME seeks to modularly optimize metabolic pathways in vitro, both speeding up the design of such systems and eliminating the issues associated with live hosts. In this review we will examine both traditional and nontraditional approaches for modular optimization, examining recent developments and discussing issues and emerging solutions for future research in metabolic engineering.

摘要

对由代谢工程微生物生产的生物产品的需求不断增加，例如药物、生物燃料、生物化学品和其他高价值化合物。为了满足这一需求，采用模块化优化，即优化子部分而不是整个系统，来设计细胞以过度生产产品。通过优化代谢途径以提高产量，模块化研究集中在传统方法上，例如 DNA、RNA 和细胞间机械的蛋白质水平模块化。虽然对这些传统方法的研究仍在继续，但规模扩大和时间成本等限制阻碍了它们的更广泛使用，同时也转向了更新颖的方法，例如从游离表达转向染色体整合。最近，正在研究非传统方法，例如共培养系统和无细胞代谢工程 (CFME)，以进行模块化优化。共培养模块性旨在最佳地划分不同宿主之间的代谢负担。CFME 寻求模块化优化代谢途径体外，既加快了此类系统的设计，又消除了与活体宿主相关的问题。在这篇综述中，我们将研究用于模块化优化的传统和非传统方法，检查最近的发展并讨论代谢工程未来研究的问题和新兴解决方案。