Metabolic Engineering:天津大学研究团队提出合成微生物组代谢调控新方案

2021-10-21作者:来源:天津大学责任编辑:食品界 字体A+AA-

微生物感应群体密度,调控自身基因表达情况和群体行为的现象称为群体感应(QS, quorum sensing)现象。群体感应系统(Quorum Sensing System)是指参与该现象的基因簇,其天然广泛存在于微生物群体中,通过以高丝氨酸内脂(AHLs)为代表的一系列小分子传递信号,在微生物种内或种间传递信息。在工业微生物领域,群体感应系统常常被用作同步裂解电路(SLC, synchronized lysis circuit)设计以及代谢波动开关(MTS, metabolic toggle swich)。

近期,天津大学研究团队Metabolic Engineering发表题为“Combinational quorum sensing devices for dynamic control in cross-feeding cocultivation”的研究成果,以异丙醇和红景天苷的微生物组为例,利用数学方法建模分析多个群体感应系统,设计了基于群体感应的微生物共培养和代谢调控方案。该研究可有效改善种间竞争关系,促进菌株的平衡生长,最终实现红景天苷等产量提升。  

该研究将群体感应系统应用于合成微生物组的共培养策略优化和代谢控制,为合成微生物组的优化改造提供了新思路。

摘要原文

Combinational quorum sensing devices for dynamic control in cross-feeding cocultivation
Shengbo Wu, Yanting Xue, Shujuan Yang, Chengyang Xu, Chunjiang Liu, Xue Liu, Jiaheng Liu, Hongji Zhu, Guang-Rong Zhao, Aidong Yang, Jianjun Qiao
Abstract
Quorum sensing (QS) offers cell density dependent dynamic regulations in cell culture through devices such as synchronized lysis circuit (SLC) and metabolic toggle switch (MTS). However, there is still a lack of studies on cocultivation with a combination of different QS-based devices. Taking the production of isopropanol and salidroside as case studies, we have mathematically modeled a comprehensive set of QS-regulated cocultivation schemes and constructed experimental combinations of QS devices, respectively, to evaluate their feasibility and optimality for regulating growth competition and corporative production. Glucose split ratio is proposed for the analysis of competition between cell growth and targeted production. Results show that the combination of different QS devices across multiple members offers a new tool with the potential to effectively coordinate synthetic microbial consortia for achieving high product titer in cross-feeding cocultivation. It is also evident that the performance of such systems is significantly affected by dynamic characteristics of chosen QS devices, carbon source control and the operational settings. This study offers insights for future applications of combinational QS devices in synthetic microbial consortia.