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Front. Microbiol. | doi: 10.3389/fmicb.2018.01671

Metabolic Engineering of Escherichia coli for Enhanced Production of Naringenin 7-sulfate and Its Biological Activities

  • 1Sun Moon University, South Korea

Flavonoids are one of the predominant groups of plant polyphenols, and these compounds have significant effects on human health and nutrition. Sulfated flavonoids have more favorable attributes compared to their parent compounds such as increased solubility, stability and bioavailability. In this research, we developed a microbial system to produce sulfated naringenin using Escherichia coli expressing a sulfotransferase from Arabidopsis thaliana (At2g03770). This wild type strain was used as a model system for testing clustered regularly interspaced short palindromic repeats (CIRSPR) interference (CRISPRi) metabolic engineering strategies. Using synthetic sgRNA to mediate transcriptional repression of cysH, a gene encoding 3´-phosphoadenosine-5´-phosphosulfate (PAPS) sulfotransferase, which is involved in sulfur metabolism, resulted in an increase in intracellular PAPS accumulation by over 3.28-fold without impairing cell growth. Moreover, naringenin 7-sulfate production by engineering E. coli with its cysH gene repressed in the open reading frame through CRISPRi was enhanced by 2.83-fold in compared with the wild type control. To improve the efficiency of biotransformation, the concentration of SO42-, glucose and substrate were optimized. The bioproductivity of naringenin 7-sulfate was 135.49 µM [~143.1 mg (47.7 mg L-1)] in a 3-L fermenter at 36 h. These results demonstrated that the CRISPRi system was successfully applied for the first time in E. coli to develop an efficient micobial strain for production of a sulfated flavonoid. In addition, antibacterial and anticancer activities of naringenin 7-sulfate were investigated and found to be higher than the parent compound.

Keywords: Sulfotranferase, CRISPRi, E. coli, PAPS, Metabolic Engineering

Received: 29 Mar 2018; Accepted: 04 Jul 2018.

Edited by:

Biswarup Mukhopadhyay, Virginia Tech, United States

Reviewed by:

Blaine Pfeifer, University at Buffalo, United States
Alvaro R. Lara, Universidad Autónoma Metropolitana, Mexico  

Copyright: © 2018 Chu, Dhakal, Shin, Jung, Yamaguchi and Sohng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Prof. Tokutaro Yamaguchi, Sun Moon University, Asan, South Korea,
Prof. Jae Kyung Sohng, Sun Moon University, Asan, South Korea,