State Key Laboratory of Biocatalysis and Enzyme Engineering, Environmental Microbial Technology Center of Hubei Province, and School of Life Sciences, Hubei University, Wuhan, China.
Xi'an Key Laboratory of C1 Compound Bioconversion Technology, School of Chemical Engineering and Technology, Xi'an Jiaotong University, Xi'an, China.
Nat Commun. 2024 Nov 30;15(1):10441. doi: 10.1038/s41467-024-54897-5.
The development and implementation of microbial chassis cells have profound impacts on circular economy. Non-model bacterium Zymomonas mobilis is an excellent chassis owing to its extraordinary industrial characteristics. Here, the genome-scale metabolic model iZM516 is improved and updated by integrating enzyme constraints to simulate the dynamics of flux distribution and guide pathway design. We show that the innate dominant ethanol pathway of Z. mobilis restricts the titer and rate of these biochemicals. A dominant-metabolism compromised intermediate-chassis (DMCI) strategy is then developed through introducing low toxicity but cofactor imbalanced 2,3-butanediol pathway, and a recombinant D-lactate producer is constructed to produce more than 140.92 g/L and 104.6 g/L D-lactate (yield > 0.97 g/g) from glucose and corncob residue hydrolysate, respectively. Additionally, techno-economic analysis (TEA) and life cycle assessment (LCA) demonstrate the commercialization feasibility and greenhouse gas reduction capability of lignocellulosic D-lactate. This work thus establishes a paradigm for engineering recalcitrant microorganisms as biorefinery chassis.
底盘细胞的开发和应用对循环经济有深远的影响。非模式菌运动发酵单胞菌由于其非凡的工业特性，是一种优秀的底盘。在这里，通过整合酶限制来模拟通量分布的动态，指导途径设计，对基因组规模代谢模型 iZM516 进行了改进和更新。我们发现，运动发酵单胞菌固有的主导乙醇途径限制了这些生物化学物质的浓度和速率。然后，通过引入低毒性但辅酶失衡的 2,3-丁二醇途径，开发了一种主导代谢受损中间底盘（DMCI）策略，并构建了一个重组 D-乳酸生产菌，从葡萄糖和玉米芯残渣水解物中分别生产出超过 140.92 g/L 和 104.6 g/L 的 D-乳酸（产率>0.97 g/g）。此外，技术经济分析（TEA）和生命周期评估（LCA）证明了木质纤维素 D-乳酸的商业化可行性和温室气体减排能力。这项工作为工程化顽固微生物作为生物炼制底盘建立了范例。
