National Key Laboratory of Enzyme and Protein Technology, University of Science, Vietnam National University, Hanoi (VNU), 334 Nguyen Trai, Thanh Xuan, Hanoi 10000, Vietnam.
Title: Engineering Escherichia coli for Biosynthesis of 4′-O-Methylresveratrol with Enhanced Anticancer Activity
Nguyen Quang Huy, Nguyen Vu Thao Tram, Nguyen Hai Ngoc, Vu Thi Dung, Duong Trang My, Ngo Thuy Duong, Nguyen Minh Thu, Quyen My Linh, Nguyen Thi An Hoa, Luan Luong Chu*
Resveratrol is a major plant stilbenoid with diverse biological and pharmaceutical activities. Its methylated derivatives often exhibit superior physicochemical and pharmacokinetic properties, including improved stability and bioavailability, relative to the parent compound. Here, we engineered Escherichia coli for the biosynthesis of 4′-O-methylresveratrol by constructing modular gene clusters comprising an O-methyltransferase from Streptomyces avermitilis (SaOMT2) and E. coli S-adenosylmethionine (SAM) synthase (EcMetK). We systematically varied the positions of T7 promoters and ribosome-binding sites (RBSs) to tune expression of each component. The resulting strain (C2), in which a dedicated T7 promoter independently regulated each gene-RBS-terminator unit, achieved a 6.1-fold increase in 4′-O-methylresveratrol production compared with the baseline strain (C0) carrying SaOMT2 alone. To further enhance biotransformation efficiency, we optimized culture media and substrate loading. Under the optimized conditions, the engineered strain produced 476.72 μM (~115.49 mg/L) 4′-O-methylresveratrol after 36 h in a 5-L fermenter. These findings support microbial production as a scalable alternative to chemical synthesis and plant extraction for resveratrol analogs. Notably, 4′-O-methylresveratrol exhibited higher anticancer activity than resveratrol, representing the first report of its activity against A549 (human lung carcinoma) and HepG2 (human hepatocarcinoma) cell lines.
Key words: Methyltransferase, Resveratrol, 4′-O-methylresveratrol, E. coli, Anticancer activity
Biography of the presenting author
Luan Luong Chu is a lecturer and researcher in Biochemistry at VNU University of Science (University of Science, Vietnam National University, Hanoi). He received his PhD from Sunmoon University (Republic of Korea). His research focuses on (i) synthetic biology and metabolic engineering for biosynthesis of bioactive compounds in genetically engineered microorganisms, (ii) discovery and study of bioactive natural products from plants, and (iii) in silico modeling and molecular docking of enzymes and pharmacologically active compounds. He has published over 40 papers in reputable journals.
Presenting author details
Full name: Luan Luong Chu
Contact number: +84-985 464 929
Email: luancl@vnu.edu.vn
Session name/ number: Medical and Pharmaceutical Biotechnology/1
Category: Poster presentation