Wang Hao, Kang Jiajia, Gao Hui
Department of Experiment and Research, South China Hospital, Medical School, Shenzhen University, Shenzhen, China.
Shenzhen Haolthy Biotechnology Co., Ltd., Shenzhen, China.
Front Bioeng Biotechnol. 2025 Apr 25;13:1529655. doi: 10.3389/fbioe.2025.1529655. eCollection 2025.
Inteins can connect flanking external proteins into a new protein fragment and excise themselves. Here, we report the splicing of proteins by engineered microbial consortia. This study pioneers a programmable microbial consortia platform enabling protein splicing through split intein-mediated assembly. Engineered with the ePop autolysis system release intein-fused protein fragments via synchronized lysis, while secretes complementary domains, enabling extracellular reconstitution directly in culture. With the application of integrating quorum-sensing controls and eukaryotic secretion pathways, this approach bypasses purification, supporting scalable one-pot synthesis of multiple functional proteins. The platform's versatility in logic computation and antibiotic resistance engineering highlights its potential for adaptive biomanufacturing and context-aware biomaterial design.
内含肽能够将侧翼的外部蛋白质连接成一个新的蛋白质片段，并自我切除。在此，我们报道了通过工程化微生物群落实现的蛋白质剪接。这项研究开创了一个可编程的微生物群落平台，能够通过分裂内含肽介导的组装实现蛋白质剪接。利用ePop自溶系统进行工程改造，通过同步裂解释放内含肽融合的蛋白质片段，同时分泌互补结构域，从而能够直接在培养物中进行细胞外重组。通过整合群体感应控制和真核分泌途径，这种方法无需纯化，支持多种功能蛋白质的可扩展一锅法合成。该平台在逻辑计算和抗生素抗性工程方面的多功能性突出了其在适应性生物制造和情境感知生物材料设计方面的潜力。
