人工多细胞体系设计与构建研究进展

Recent research progress in the design and construction of synthetic microbial consortia

合成生物学的发展正从优化基因元件与模块走向从头设计复杂代谢线路。多细胞体系因可实现代谢功能分工、复杂底物多组分利用及耐受复杂环境等,在医药、食品、化工、环境及能源等领域发挥着不可替代的作用,并已成为合成生物学发展的新方向。然而,多细胞体系的研究还处于起步阶段,理性设计与构建人工多细胞体系、解析细胞间信息互作机制及调控多细胞体系结构等方面还面临诸多挑战。本文综述了人工多细胞体系在医药开发与医疗健康、天然产物合成、木质纤维素一体化生物加工以及环境修复等领域的应用,总结了人工多细胞体系的构建原理,阐述了多细胞体系内细胞间的交流机制,并剖析了人工多细胞体系面临的诸多挑战以及针对性的解决方案,为构建系统鲁棒、稳定、可控的人工多细胞体系提供理论指导。

Synthetic biology is developed from designing and building simple elements and modules to de novo buildup complex metabolic pathway and network.Recent advances in microbial consortia present a valuable approach for expanding the scope of synthetic biology.First,microbial consortia can create a novel microenvironment for strains,potentially resulting in the activation of silent metabolic pathways which are not expressed under"normal"cultivation conditions,leading to discovery of novel chemicals for novel drugs and other purposes;Second,microbial consortia allow a labor division for metabolic modules among different microbial strains,which permit improved efficiency and more complex behavior than monocultures;Third,microbial consortia consist of multiple functional microorganisms,allowing capability for utilizing complex substrate with robust tolerance to environmental stresses.All these endow microbial consortia an indispensible role in the areas of medicine,food,chemical engineering,energy industry and biodegradation for environmental pollutants.However,the study of synthetic microbial consortia is still in its infancy,facing many unknowns and challenges in the construction of stable and controllable microbial consortia systems,intercellular communication and regulation of microbial population structure.This review summarizes the application of synthetic microbial consortia in the areas of human health monitoring and medicine exploitation,synthesis of valuable compounds,consolidated bioprocessing of lignocellulosic materials and environmental bioremediation,as well as the construction principles and research methods for microbial consortia study.In addition,the unrevealed interaction mechanism underlying microbial consortia is addressed.Moreover,the outstanding challenges and future directions to advance the development of high-efficient,stable and controllable synthetic microbial consortia are highlighted.