Establishing a synergetic carbon utilization mechanism for non-catabolic use of glucose in microbial synthesis of 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.
State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing 100029, China.
Yifei
Y
Wu
State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing 100029, China.
Xinxiao
X
Sun
College of Engineering, The University of Georgia, Athens, GA 30602, USA.
Yuheng
Y
Lin
State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing 100029, China.
Xiaolin
X
Shen
College of Engineering, The University of Georgia, Athens, GA 30602, USA.
Yaping
Y
Yang
College of Engineering, The University of Georgia, Athens, GA 30602, USA.
Rachit
R
Jain
State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing 100029, China. Electronic address: yuanqp@mail.buct.edu.cn.
Qipeng
Q
Yuan
College of Engineering, The University of Georgia, Athens, GA 30602, USA. Electronic address: yajunyan@uga.edu.
Yajun
Y
Yan
D053898:Biosynthetic Pathways / Q000502:physiology; D002244:Carbon / Q000378:metabolism*; D049109:Cell Proliferation / Q000502:physiology; D003198:Computer Simulation; D004926:Escherichia coli / Q000502:physiology*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D005947:Glucose / Q000235:genetics / Q000378:metabolism*; D005990:Glycerol / Q000378:metabolism; D060847:Metabolic Engineering / Q000379:methods*; D064688:Metabolic Flux Analysis / Q000379:methods; D053858:Metabolic Networks and Pathways / Q000502:physiology; D008660:Metabolism / Q000502:physiology; D008954:Models, Biological; D014199:Trehalose / Q000096:biosynthesis* / Q000235:genetics / Q000302:isolation & purification
D029968:Escherichia coli Proteins; D002244:Carbon; D014199:Trehalose; D005947:Glucose; D005990:Glycerol
Carbon utilization; Glycosylation; Polysaccharide; Trehalose; UDP-glucose