Genetic controllers for enhancing the evolutionary longevity of synthetic gene circuits in bacteria

• 全文链接

用于提高细菌合成基因回路进化寿命的遗传控制器

关键词：

来源：

Nature Communications

全文链接：

//agri.nais.net.cn/topic/downloadFile/80934a40-430b-4cbe-b9e8-d6b484bc295a

来源地址：

https://www.nature.com/articles/s41467-025-63627-4

资源所属：

马铃薯基因组设计育种

类型：

学术文献

语种：

英语

原文发布日期：

2025-09-29

摘要：

Engineered gene circuits often degrade due to mutation and selection, limiting their long-term utility. Here we present designs for genetic controllers which maintain synthetic gene expression over time. Using a multi-scale “host-aware" computational framework, which captures interactions between host and circuit expression, mutation, and mutant competition, we evaluate several controller architectures based on three metrics for evolutionary stability: total protein output, duration of stable output, and half-life of production. We propose a number of designs with varying inputs (e.g., output per cell, growth rate) and actuation methods (transcriptional vs. post-transcriptional regulation). We find post-transcriptional controllers generally outperform transcriptional ones, but no single design optimizes all goals. Negative autoregulation prolongs short term performance, while growth-based feedback extends functional half-life. We propose three biologically feasible, multi-input controllers that improve circuit half-life over threefold without requiring coupling the process to an essential gene or a genetic kill switch.