Engineering <i>Escherichia coli</i> for autoinducible production of L-valine: An example of an artificial positive feedback loop in amino acid biosynthesis

Artificial metabolically regulated inducible expression systems are often used for the production of essential compounds. In most cases, the application of such systems enables regulating the expression of an entire group of genes in response to any internal signal such as an aerobic/anaerobic switch, a transition to stationary phase, or the exhausting of essential compounds. In this work, we demonstrate an example of another type of artificial autoinducible module, denoted a positive feedback module. This positive feedback module generates an inducer molecule that in turn enhances its own synthesis, promoting an activation signal. Due to the use of acetolactate, an intermediate of the L-valine biosynthetic pathway, as a specific inducer molecule, we realized a positive feedback loop in the biosynthetic pathway of branched chain amino acids. Such positive feedback was demonstrated to improve the production of a target compound.人工代谢调控型诱导表达系统（artificial metabolically regulated inducible expression systems）常用于必需化合物的生产。在多数场景中，这类系统可通过响应内部信号（如有氧/厌氧转换、进入稳定生长期、必需化合物耗尽等）来调控一整组基因的表达。本研究中，我们展示了另一类人工自诱导模块的实例——正反馈模块（positive feedback module）。该正反馈模块可生成诱导分子，而该诱导分子又会反过来增强自身的合成，从而强化激活信号。由于我们以L-缬氨酸生物合成途径的中间产物乙酰乳酸作为特异性诱导分子，最终在支链氨基酸的生物合成通路中构建了正反馈环路。实验证明，这类正反馈可提升目标化合物的产量。