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Front. Bioeng. Biotechnol. | doi: 10.3389/fbioe.2019.00351

Metabolic engineering of Escherichia coli for the production of hyaluronic acid from glucose and galactose

Ji Eun Woo1, Hyeon Jeong Seong1,  Sang Yup Lee2* and  Yu-Sin Jang1, 3*
  • 1Department of Agricultural Chemistry and Food Science Technology, Division of Applied Life Science (BK21 Plus Program), Institute of Agriculture & Life Science (IALS), Gyeongsang National University, South Korea
  • 2Department of Chemical and Biomolecular Engineering (BK21 Plus Program), BioProcess Engineering Research Center, Center for Systems and Synthetic Biotechnology, Institute for the BioCentury, KAIST, South Korea
  • 3Gyeongsang National University, South Korea

Hyaluronic acid is a glycosaminoglycan biopolymer widely present throughout connective and epithelial tissue, and has been of great interest for medical and cosmetic applications. In the microbial production of hyaluronic acid, it has not been established to utilize galactose enabling to be converted to UDP-glucuronic acid, which is a precursor for hyaluronic acid biosynthesis. In this study, we engineered Escherichia coli to produce hyaluronic acid from glucose and galactose. The galactose-utilizing Leloir pathway was activated by knocking out the galR and galS genes encoding the transcriptional repressors. Also, the hasA gene from Streptococcus zooepidemicus was introduced for the expression of hyaluronic acid synthase. The consumption rates of glucose and galactose were modulated by knockout of the pfkA and zwf genes, which encode 6-phosphofructokinase I and glucose-6-phosphate dehydrogenase, respectively. Furthermore, the precursor biosynthesis pathway for hyaluronic acid production was manipulated by separately overexpressing the gene clusters galU-ugd and glmS-glmM-glmU, which enable the production of UDP-glucuronic acid and UDP-N-acetyl-glucosamine, respectively. Batch culture of the final engineered strain produced 29.98 mg/L of hyaluronic acid from glucose and galactose. This study demonstrated the production of hyaluronic acid from glucose and galactose in the engineered E. coli.

Keywords: Hyaluronic Acid, Galactose, Escherichia coli, UDP-N-acetyl glucosamine, UDP-glucuronic acid

Received: 06 Sep 2019; Accepted: 06 Nov 2019.

Copyright: © 2019 Woo, Seong, Lee and Jang. 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. Sang Yup Lee, Department of Chemical and Biomolecular Engineering (BK21 Plus Program), BioProcess Engineering Research Center, Center for Systems and Synthetic Biotechnology, Institute for the BioCentury, KAIST, Daejeon, South Korea, leesy@kaist.ac.kr
Prof. Yu-Sin Jang, Gyeongsang National University, Jinju, South Korea, jangys@gnu.ac.kr