面向应用的合成微生物群落鲁棒性及设计原则

齐泮晴; 刘学文; 吴梦迪; 侯启会; 聂勇; 吴晓磊; 马安周

doi:10.12211/2096-8280.2026-043

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面向应用的合成微生物群落鲁棒性及设计原则

特约评述 | 更新时间：2026-08-04

- 面向应用的合成微生物群落鲁棒性及设计原则
- Robustness and design principles of synthetic microbial communities for application
- 合成生物学 2026年页码：1-16
- 作者机构：
  
  1.中国科学院生态环境研究中心，北京 100085
  2.中国科学院大学，资源与环境学院，北京 100049
  3.北京大学，力学与工程科学学院，北京 100871
  4.香港中文大学，物理系，香港 999077
- 作者简介：
  
  齐泮晴（1992—），男，博士，助理研究员。研究方向为油藏环境微生物。
  马安周（1980—），男，博士，研究员，博士生导师，研究方向为环境微生物生态适应机制。
- 基金信息：
  
  国家重点研发计划(2024YFA0919000);国家自然科学基金(32400102)
- DOI：10.12211/2096-8280.2026-043
  中图分类号： T-012
- 收稿：2026-05-14，
  
  修回：2026-07-31，
  
  网络首发：2026-08-04，
- 稿件说明：
移动端阅览
齐泮晴，刘学文，吴梦迪，侯启会，聂勇，吴晓磊，马安周. 面向应用的合成微生物群落鲁棒性及设计原则［J］. 合成生物学， 2026， 7. DOI： 10.12211/2096-8280.2026-043

Qi Panqing， Liu Xuewen， Wu Mengdi， Hou Qihui， Nie Yong， Wu Xiaolei， Ma Anzhou. Robustness and design principles of synthetic microbial communities for application［J］. Synthetic Biology Journal， 2026， 7. DOI： 10.12211/2096-8280.2026-043
齐泮晴，刘学文，吴梦迪，侯启会，聂勇，吴晓磊，马安周. 面向应用的合成微生物群落鲁棒性及设计原则［J］. 合成生物学， 2026， 7. DOI： 10.12211/2096-8280.2026-043 DOI：

Qi Panqing， Liu Xuewen， Wu Mengdi， Hou Qihui， Nie Yong， Wu Xiaolei， Ma Anzhou. Robustness and design principles of synthetic microbial communities for application［J］. Synthetic Biology Journal， 2026， 7. DOI： 10.12211/2096-8280.2026-043 DOI：

摘要

合成微生物群落（Synthetic microbial communities， SynComs）作为合成生物学从单细胞工厂向多细胞群体协作范式转变的核心载体，是实现复杂工程化功能的重要策略。然而，当合成微生物群落从可控的实验室环境转移至复杂、异质的开放生境时，其群落组成与功能的维持能力（即鲁棒性/稳健性，Robustness）往往显著降低。本文首先从环境适配性、功能稳定性、定植稳定性及尺度扩展性四个维度，系统解构了应用场景下合成微生物群落鲁棒性的多维内涵。为应对开放环境的复杂性，并规避低复杂度合成微生物群落（通常含20个以下物种）涌现特性固有的局限性，本文以能够模拟自然生境复杂性的大规模合成微生物群落（含20个以上物种）为研究模型，通过逆向工程解析其在波动压力下维持鲁棒性的深层机制。分析表明，大规模合成微生物群落的鲁棒性源于非线性耦合所产生的涌现特性：在系统发育维度，高丰度物种间的多样性冗余构筑了严密的生态位屏障，显著增强入侵防御能力；在代谢维度，群落成员构建了高效的负反馈回路，关键物种的代谢汇功能有效缓解了有害中间产物的毒性积累；在环境响应维度，群落与宿主调控及生境波动表现出强相关性。值得注意的是，现有研究还表明定植能力与功能表现之间存在解耦现象，即合成微生物群落的功能鲁棒性可在不依赖永久性生态位占据的前提下，以瞬时、即时性的效应形式呈现。基于上述认识，本文提出了面向合成微生物群落应用的四项理性设计原则：1）系统发育维度的生态位饱和原则——通过在目标场景中最大化谱系饱和度以增强入侵抗性；2）代谢负反馈原则——利用关键代谢汇物种消除代谢毒性；3）宿主维度的环境耦合原则——实现合成微生物群落与土著环境因子的稳态匹配；4）功能需求驱动的效应权衡原则——作为顶层约束，该原则主张依据具体应用场景（如即时干预型与长期维持型）动态调整其他原则的设计逻辑。本综述为合成微生物群落跨越实验室至开放生境的尺度障碍提供了关键的方法学指引，同时为强化"设计-构建-测试-学习"（DBTL）循环的底层约束及理性构建高性能、高稳定性合成微生物群落指明了可供参考的优化路径。

Abstract

Synthetic microbial communities (SynComs)

serving as the core vehicle for the paradigm shift in synthetic biology from monoculture cell factories to multicellular consortia

represent a pivotal strategy for achieving complex functionalities. However

a significant robustness gap persists when transitioning SynComs from controlled laboratory settings to complex

heterogeneous open environments. This review first systematically deconstructs the multidimensional connotations of robustness of SynComs for application across four key dimensions: environmental fitness

functional stability

colonization persistence

and scale-up adaptability. To address the complexity of open environments and circumvent the inherent limitations of emergent properties in low-complexity SynComs (typically comprising fewer than 20 species)

this review employs high-complexity

large-scale SynComs (comprising more than 20 species)

designed for high-fidelity emulation of complex natural habitats

as research models. Through reverse engineering

we characterize the underlying ecological mechanisms that maintain robustness under fluctuating pressures. Our analysis reveals that the robustness of large-scale SynComs originates from emergent properties generated by nonlinear coupling. In the phylogenetic dimension

diversity redundancy among high-abundance species forms a rigorous niche barrier

significantly enhancing invasive defense. In the metabolic dimension

members of SynComs construct efficient negative feedback loops

where the metabolic sink function of key species effectively alleviates the toxic accumulation of hazardous intermediates. In the environmental response dimension

the consortia exhibit strong correlations with host regulation and habitat fluctuations. Crucially

existing studies have indicated a decoupling between colonization and function

demonstrating that the functional robustness of SynComs can manifest as transient and immediate effects

rather than relying on permanent niche occupation. Based on these insights

we propose four rational design principles for the application of SynComs: 1) Phylogenetic niche saturation

enhancing invasion resistance by maximizing lineage saturation in target scenarios; 2) Metabolic negative feedback regulation

utilizing key metabolic sink species to eliminate metabolic toxicity; 3) Host-environment coupling

achieving steady-state alignment between artificial consortia and indigenous environmental factors; and 4) Functional demand-driven effect trade-offs. Functioning as a top-level constraint

this principle advocates for the dynamic adjustment of design logic across the other principles based on specific application scenarios (e.g.

immediate intervention vs. long-term maintenance). This review provides systematic methodological guidance for the application of SynComs to overcome scale barriers when transitioning from the laboratory to open environments. Furthermore

it offers robust theoretical support for strengthening the underlying constraints of the "Design-Build-Test-Learn" (DBTL) cycle and for the rational construction of high-performance

stable SynComs.

关键词

Keywords

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