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Production of caffeoylmalic acid from glucose in engineered Escherichia coli

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Abstract

Objectives

To achieve biosynthesis of caffeoylmalic acid from glucose in engineered Escherichia coli.

Results

We constructed the biosynthetic pathway of caffeoylmalic acid in E. coli by co-expression of heterologous genes RgTAL, HpaBC, At4CL2 and HCT2. To enhance the production of caffeoylmalic acid, we optimized the tyrosine metabolic pathway of E. coli to increase the supply of the substrate caffeic acid. Consequently, an E. coliE. coli co-culture system was used for the efficient production of caffeoylmalic acid. The final titer of caffeoylmalic acid reached 570.1 mg/L.

Conclusions

Microbial production of caffeoylmalic acid using glucose has application potential. In addition, microbial co-culture is an efficient tool for producing caffeic acid esters.

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Acknowledgement

This work was supported by grants from the National Natural Science Foundation of China (Nos. 31770104, 21302214), the Key Deployment Project of CAS (No. KFZD-SW-215) and the Youth Innovation Promotion Association CAS (2017207).

Supporting information

Supplementary Table 1—Plasmids and strains used in this study.

Supplementary Table 2—Primers used in this study.

Supplementary Fig. 1—HPLC analysis of the production of p-coumaric acid in strains BW01 and BW02.

Supplementary Fig. 2—HPLC analysis of the production of caffeic acid in strains BW03 and BTAL01

Supplementary Fig. 3—Comparation of the production of p-coumaric acid and caffeic acid in E. coli BL21 (DE3).

Supplementary Fig. 4—1H and 13C NMR spectrum of isolated caffeoylmalic acid in CD3OD.

Supplementary Fig. 5—Time profile of cell growth of BTAL01 and BTAL02.

Supplementary Fig. 6—E. coliE. coli co-culture system for efficient production of caffeoylmalic acid.

Supplementary Fig. 7—HPLC analysis of the products in the fermentation supernatant of the co-cultures with the inoculum ratio of 6:1.

Supplementary Fig. 8—Time profiles of cell growth of the co-culture system.

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Correspondence to Tao Liu.

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Li, T., Zhou, W., Bi, H. et al. Production of caffeoylmalic acid from glucose in engineered Escherichia coli. Biotechnol Lett 40, 1057–1065 (2018). https://doi.org/10.1007/s10529-018-2580-x

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  • DOI: https://doi.org/10.1007/s10529-018-2580-x

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