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Establishing a synergetic carbon utilization mechanism for non-catabolic use of glucose in microbial synthesis of trehalose

Wu, Yifei, Sun, Xinxiao, Lin, Yuheng, Shen, Xiaolin, Yang, Yaping, Jain, Rachit, Yuan, Qipeng, Yan, Yajun
Metabolic engineering 2017 v.39 pp. 1-8
biosynthesis, carbon, cell growth, energy, glucose, glycerol, glycosylation, metabolites, models, polysaccharides, trehalose
In nature glucose is a common carbon and energy source for catabolic use and also a building unit of polysaccharides and glycosylated compounds. The presence of strong glucose catabolic pathways in microorganism rapidly decomposes glucose into smaller metabolites and challenges non-catabolic utilization of glucose as C6 building unit or precursor. To address this dilemma, we design a synergetic carbon utilization mechanism (SynCar), in which glucose catabolism is inactivated and a second carbon source (e.g. glycerol) is employed to maintain cell growth and rationally strengthen PEP driving force for glucose uptake and non-catabolic utilization. Remarkably, a trehalose biosynthesis model developed for proof-of-concept indicates that SynCar leads to 131% and 200% improvement in trehalose titer and yield, respectively. The conversion rate of glucose to trehalose reaches 91% of the theoretical maximum. This work demonstrates the broad applicability of SynCar in the biosynthesis of molecules derived from non-catabolic glucose.