Convergent engineering of syntrophic Escherichia coli coculture for efficient production of glycosides

• Published in: Metabolic engineering Vol. 47; pp. 243 - 253
• Main Authors: Liu, Xue, Li, Xiao-Bo, Jiang, Jianlan, Liu, Zhen-Ning, Qiao, Bin, Li, Fei-Fei, Cheng, Jing-Sheng, Sun, Xiaocui, Yuan, Ying-Jin, Qiao, Jianjun, Zhao, Guang-Rong
• Format: Journal Article
• Language: English
• Published: Belgium Elsevier Inc 01.05.2018
• Subjects: Co-culture; Coculture; Consortium; Escherichia coli; Escherichia coli - genetics; Escherichia coli - growth & development; Glucosides - biosynthesis; Glucosides - genetics; Glycoside; Metabolic Engineering; Phenols; Phenylethyl Alcohol - analogs & derivatives; Phenylethyl Alcohol - metabolism; Salidroside; Synthetic biology; Uridine Diphosphate Glucose - genetics; Uridine Diphosphate Glucose - metabolism; Xylose - genetics; Xylose - metabolism; Salidroside; Coculture; Escherichia coli; Consortium; Metabolic engineering; Glycoside; Synthetic biology; Co-culture
• ISSN: 1096-7176; 1096-7184
• DOI: 10.1016/j.ymben.2018.03.016

Synthetic microbial coculture to express heterologous biosynthetic pathway for de novo production of medicinal ingredients is an emerging strategy for metabolic engineering and synthetic biology. Here, taking efficient production of salidroside as an example of glycosides, we design and construct a syntrophic Escherichia coli-E. coli coculture composed of the aglycone (AG) strain and the glycoside (GD) strain, which convergently accommodate biosynthetic pathways of tyrosol and salidroside, respectively. To accomplish this the phenylalanine-deficient AG strain was engineered to utilize xylose preferentially and to overproduce precursor tyrosol, while the tyrosine-deficient GD strain was constructed to consume glucose exclusively and to enhance another precursor UDP-glucose availability for synthesis of salidroside. The AG and GD strains in the synthetic consortium are obligatory cooperators through crossfeeding of tyrosine and phenylalanine and compatible in glucose and xylose mixture. Through balancing the metabolic pathway strength, we show that the syntrophic coculture was robust and stable, and produced 6.03 g/L of salidroside. It was the de novo production of salidroside for the first time in E. coli coculture system, which would be applicable for production of other important glycosides and natural products. •Metabolic engineering of E. coli coculture for efficient production of salidroside.•Escherichia coli-E. coli metabolically engineered to syntrophic coculture.•Synthetic Escherichia coli-E. coli coculture for production of glycosides.•Crossfeeding of tyrosine and phenylalanine made syntrophic consortium.•Convergent assembly of salidroside metabolic pathway into separate strains.