克雷伯氏肺炎杆菌LDH526产1,3-丙二醇的甘油自动流加策略

Automatically feeding strategy for 1,3-propanediol fermentation of Klebsiella pneumoniae LDH526

摘要:

1,3-丙二醇是一种重要的化工原料，主要作为平台化合物用于合成聚酯，如聚对苯二甲酸丙二醇酯。经基因工程改造的克雷伯氏肺炎杆菌LDH526能以甘油作为唯一碳源合成1,3-丙二醇，最终发酵浓度超过90 g/L。甘油浓度是影响1,3-丙二醇合成的关键因素。为了实现对甘油浓度的精确控制，设计并优化了基于发酵动力学的甘油自动流加策略。通过将底物流加速率与易观察变量pH和发酵时间偶联，实现了发酵过程中甘油流加的自启动和甘油浓度的动态控制。发酵72 h，1,3-丙二醇的浓度可稳定超过95 g/L。自动控制甘油流加的发酵过程具有可重复性、连续性以及人工工作量少的特点，有望从实验室规模扩大到生产规模。

Abstract:

1,3-propandiol is an important chemical used as building block for the synthesis of highly promising polyesters such as polytrimethylene terephthalate. A genetically modified Klebsiella pneumoniae LDH526 can use glycerol as sole carbon source and produce 1,3-propanediol with the titer above 90 g/L. A key factor affecting the production of 1,3-propanediol by the mutant K. pneumoniae is the accurate control of the feeding of glycerol. To generate a robust and reproducible fermentation process of 1,3-propanediol, we designed and optimized an automatically feeding strategy of glycerol based on fermentation kinetics. By coupling the substrate feeding rate with easily observed variables -pH and fermentation time, we have achieved self-starting glycerol feeding and dynamic control of the glycerol concentration during the fermentation process. This automated system allowed us to generate a reproducible, consistent and operator-independent process from lab-scale to production scale. The final concentration of 1,3-propaediol was above 95 g/L after 72 h.