Zhang Lifang, Bryan Samantha J, Selão Tiago Toscano
Department of Chemical and Environmental Engineering, University of Nottingham, Nottingham, United Kingdom.
Front Microbiol. 2022 Aug 17;13:973244. doi: 10.3389/fmicb.2022.973244. eCollection 2022.
Citric acid is one of the most widely used organic acids in the world, with applications ranging from acidity regulation in food and beverages to metal chelation in hydrometallurgical processes. Most of its production is currently derived from fermentative processes, using plant-derived carbon feedstocks. While these are currently dominant, there is an increasing need to develop closed-loop production systems that reduce process carbon footprint. In this work, we demonstrate for the first time that an engineered marine cyanobacterium sp. PCC 7002 can be used as a sustainable chassis for the photosynthetic conversion of CO to citric acid. Decreased citric acid cycle flux, through the use of a theophylline-responsive riboswitch, was combined with improved flux through citrate synthase and enhanced citric acid excretion, resulting in a significant improvement to citric acid production. While allowing citrate production, this strategy induces a growth defect which can be overcome by glutamate supplementation or by fine-tuning aconitase levels, resulting in an increase in production relative to WT of over 100-fold. This work represents a first step toward sustainable production of a commodity organic acid from CO.
柠檬酸是世界上使用最广泛的有机酸之一，其应用范围从食品和饮料的酸度调节到湿法冶金过程中的金属螯合。目前其大部分生产来自发酵过程，使用植物源碳原料。虽然这些目前占主导地位，但越来越需要开发减少工艺碳足迹的闭环生产系统。在这项工作中，我们首次证明了工程化的海洋蓝藻菌株PCC 7002可以用作将CO光合转化为柠檬酸的可持续底盘。通过使用茶碱响应性核糖开关降低柠檬酸循环通量，与通过柠檬酸合酶提高通量和增强柠檬酸排泄相结合，从而显著提高了柠檬酸产量。虽然允许柠檬酸盐产生，但这种策略会导致生长缺陷，这可以通过补充谷氨酸或微调乌头酸酶水平来克服，从而使产量相对于野生型提高100倍以上。这项工作代表了从CO可持续生产商品有机酸的第一步。
