人工合成微生物组的构建与应用

徐昭勇, 胡海洋, 许平, 唐鸿志

合成生物学 ›› 2021, Vol. 2 ›› Issue (2): 181-193.doi: 10.12211/2096-8280.2020-062

摘要：

近年来，随着微生物组学、计算生物学、合成生物学等研究的迅猛发展，人工构建高效稳定的人工菌群逐渐成为研究热点，从而衍生出新的研究领域，被称为合成微生物组。合成微生物组的研究，是通过对不同的微生物菌株进行整合，高效、稳定、安全地处理更复杂的任务，完成单一菌株无法完成的目标，从而满足更广泛的需要。本文简述了构建合成微生物组需要遵循的基本原则、四种策略，回答如何构建微生物组的问题，介绍了“自下而上”和“自上而下”两种构建合成微生物组的方法，回顾了合成微生物组在工业生产和环境修复领域的具体应用，例如生物能源、化工产品、生物医药的合成，以及石油、石油衍生物、农药等污染物的生物修复，为微生物技术的实际应用开拓了新的方向。最后，通过综合分析表明，挖掘代谢信息明确的合成微生物组底盘菌株并加以遗传改造，使其适应更复杂的环境，将是未来的研究重点。

关键词: 合成微生物组, 合成生物学, 生物合成, 生物修复, 生物安全

Abstract:

In recent years, the construction of artificial bacterial communities, usually referred to "synthetic” or “engineered” microbiomes, with better attributes and stability, has been a hot topic. The archetype synthetic community integrates different strains by balancing their nutrition, which occurs when strains produce and consume essential nutrients in a complementary fashion. Other key features of synthetic communities include: reciprocal interactions of metabolic pathways. On the one hand, complete metabolic pathways may develop only at the population level, and the metabolic burden on any single strain can reduce. On the other hand, growth inhibition can relief, since metabolites of one strain promote the growth of another, and reduction of the mutation rate guarantees a stable community. When combined, these features ensure intercellular interactions, spatiotemporal organization, community robustness, and biocontainment of synthetic communities. There are two general approaches for engineering microbiomes. One is "bottom-up", through which genetic circuits involving different strains are designed artificially. This approach can be more controllable, but the precise knowledge of metabolic pathway details is needed. Another approach, known as "top-down", involves the careful optimization of a core consortium from a group of natural microbiomes which can be easier to carry out, but is less designable. Synthetic microbiomes can be expected to handle complex tasks more efficiently, stably, and safely, which show a series of special characters compared with one single strain, such as apparent metabolic burden reduction and offering a platform with excellent compatibility for the expression of diverse genes. By now, the synthetic microbiome approach has already been applied to industrial production and environmental remediation, such as the biosynthesis of biofuels, chemical products, and biomedicines, and for the bioremediation of petroleum contamination and residues of petroleum derivatives and pesticides. Synthetic microbiomes open a new direction for applications of microbial technology with improved stability and compatibility. This approach could be used to enhance the roles of particularly valuable strains, helping to extend their applications to more complicated tasks in extreme environments.

Key words: synthetic microbiome, synthetic biology, biosynthesis, bioremediation, biosecurity