title: Microbial production of astilbin, a bioactive rhamnosylated flavanonol, from taxifolin.
abstract: Flavonoids are plant-based polyphenolic biomolecules with a wide range of biological activities. Glycosylated flavonoids have drawn special attention in the industries as it improves solubility, stability, and bioactivity. Herein, we report the production of astilbin (ATN) from taxifolin (TFN) in genetically-engineered Escherichia coli BL21(DE3). The exogenously supplied TFN was converted to ATN by 3-O-rhamnosylation utilizing the endogeneous TDP-L-rhamnose in presence of UDP-glycosyltransferase (ArGT3, Gene Bank accession number: At1g30530) from Arabidopsis thaliana. Upon improving the intracellular TDP-L-rhamnose pool by knocking out the chromosomal glucose phosphate isomerase (pgi) and D-glucose-6-phosphate dehydrogenase (zwf) deletion along with the overexpression of rhamnose biosynthetic pathway increases the biotransformation product, ATN with total conversion of ~49.5 ± 1.67% from 100 µM of taxifolin. In addition, the cytotoxic effect of taxifolin-3-O-rhamnoside on PANC-1 and A-549 cancer cell lines was assessed for establishing ATN as potent antitumor compound.
authors.affiliation: Center for Molecular Biology, Institute of Research and Development, Duy Tan University, K7/25 Quang Trung, Danang, Vietnam. thuanbiochem@gmail.com.
authors.forename: Nguyen Huy
authors.initials: NH
authors.lastname: Thuan
authors.affiliation: Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kemitorvet, 2800, Kongens Lyngby, Denmark.
authors.forename: Sailesh
authors.initials: S
authors.lastname: Malla
authors.affiliation: Center for Molecular Biology, Institute of Research and Development, Duy Tan University, K7/25 Quang Trung, Danang, Vietnam.
authors.forename: Nguyen Thanh
authors.initials: NT
authors.lastname: Trung
authors.affiliation: Department of Life Science and Biochemical Engineering, SunMoon University, 70 Sunmoon-ro 221, Tangjeong-myeon, Asan-si, Chungnam, 31460, Republic of Korea.
authors.forename: Dipesh
authors.initials: D
authors.lastname: Dhakal
authors.affiliation: Department of Life Science and Biochemical Engineering, SunMoon University, 70 Sunmoon-ro 221, Tangjeong-myeon, Asan-si, Chungnam, 31460, Republic of Korea.
authors.forename: Anaya Raj
authors.initials: AR
authors.lastname: Pokhrel
authors.affiliation: Department of Life Science and Biochemical Engineering, SunMoon University, 70 Sunmoon-ro 221, Tangjeong-myeon, Asan-si, Chungnam, 31460, Republic of Korea.
authors.forename: Luan Luong
authors.initials: LL
authors.lastname: Chu
authors.affiliation: Department of Life Science and Biochemical Engineering, SunMoon University, 70 Sunmoon-ro 221, Tangjeong-myeon, Asan-si, Chungnam, 31460, Republic of Korea. sohng@sunmoon.ac.kr.|Department of BT-Convergent Pharmaceutical Engineering, SunMoon University, 70 Sunmoon-ro 221, Tangjeong-myeon, Asan-si, Chungnam, 31460, Republic of Korea. sohng@sunmoon.ac.kr.
authors.forename: Jae Kyung
authors.initials: JK
authors.lastname: Sohng
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D029681:Arabidopsis Proteins / Q000235:genetics / Q000378:metabolism; D053898:Biosynthetic Pathways; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D044948:Flavonols / Q000096:biosynthesis*; D055786:Gene Knockout Techniques; D005818:Genetic Engineering / Q000379:methods; D006031:Glycosylation; D016695:Glycosyltransferases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D011794:Quercetin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D012210:Rhamnose / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D029681:Arabidopsis Proteins; D044948:Flavonols; C099069:astilbin; D011794:Quercetin; C003377:taxifolin; D016695:Glycosyltransferases; D012210:Rhamnose
keywords: Biotransformation; Cytotoxicity; Escherichia coli; Flavonoid; Glycosylation