Enzymatic synthesis of myricetin 3- O-galactoside through a whole-cell biocatalyst

Zhen Xu; Wei-Qing He; Chun-Sheng Liu; Jian-Qiang Kong

doi:10.1016/j.chmed.2020.03.009

Enzymatic synthesis of myricetin 3- O-galactoside through a whole-cell biocatalyst

Chin Herb Med. 2020 Oct 16;12(4):384-389. doi: 10.1016/j.chmed.2020.03.009. eCollection 2020 Oct.

Authors

Zhen Xu^{1

2}, Wei-Qing He³, Chun-Sheng Liu², Jian-Qiang Kong¹

Affiliations

¹ State Key Laboratory of Bioactive Substance and Function of Natural Medicines & NHC Key Laboratory of Biosynthesis of Natural Products, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
² School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China.
³ NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.

Abstract

Objective: Myricetin 3-O-galactoside is an active compound with pharmaceutical potential. The insufficient supply of this compound becomes a bottleneck in the druggability study of myricetin 3-O-galactoside. Thus, it is necessary to develop a biosynthetic process for myricetin 3-O-galactoside through metabolic engineering.

Methods: Two genes OcSUS1 and OcUGE1 encoding sucrose synthase and UDP-glucose 4-epimerase were introduced into BL21(DE3) to reconstruct a UDP-D-galactose (UDP-Gal) biosynthetic pathway in Escherichia coli. The resultant chassis strain was able to produce UDP-Gal. Subsequently, a flavonol 3-O-galactosyltransferase DkFGT gene was transformed into the chassis strain producing UDP-Gal. An artificial pathway for myricetin 3-O-galactoside biosynthesis was thus constructed in E. coli.

Results: The obtained engineered strain was demonstrated to be capable of producing myricetin 3-O-galactoside, reaching 29.7 mg/L.

Conclusion: Biosynthesis of myricetin 3-O-galactoside through engineered E. coli could be achieved. This result lays the foundation for the large-scale preparation of myricetin 3-O-galactoside.

Keywords: engineered Escherichia coli; flavonol 3-O-galactosyltransferase; galactosyltransferase; myricetin 3-O-galactoside.